! " ! # $ # % & ' $ " ( #" &# # ## # # # & # $# $ ' " " ( $& # #"& # ## $# !#) $#( # # ( # # ) # & ! $ # " ! " % # "$ ! $ $" # " $ $ % ! $#( ## & " " # " ) &" $ & " '* ""& " $ + , &" , - #& * # ') ! ! " # $!% ! & $ ' ' ($ ' #% % )%*%' $ ' +"%& '! # $, ($ % ! % ! % % "# % %#%%"#$% ! % ! ""## -$$$ . /"/"#012" ".")*3- +) *!4!& 5!6%55787&%% 0! 9! *& * !"!#$!%&%$!' -:&'()*+),-*&');8<78".")*3- +) "1 '"" &8<78 ɈȽɅȺȼɅȿɇɂȿ ȼȼȿȾȿɇɂȿ……………………………………………………………3 1. ɉɊɈɌȿɈɆɂɄȺ ɂ ɉɈɌȿɇɐɂȺɅ ɋɌȼɈɅɈȼɕɏ ɄɅȿɌɈɄ ȾɅə ɌȿɊȺɉɂɂ ȺɌȿɊɈɋɄɅȿɊɈɁȺ………………………………9 1.1. ɉɪɨɬɟɨɦɢɤɚ ɤɚɤ ɢɧɫɬɪɭɦɟɧɬ ɢɡɭɱɟɧɢɹ ɤɥɟɬɨɤ…………………... 9 1.2. ɋɬɜɨɥɨɜɵɟ ɤɥɟɬɤɢ, ɚɬɟɪɨɫɤɥɟɪɨɡ ɢ ɩɪɨɬɟɨɦɢɤɚ.……………..14 1.3. Ƚɟɦɨɩɨɷɬɢɱɟɫɤɢɟ ɫɬɜɨɥɨɜɵɟ ɤɥɟɬɤɢ ɤɚɤ ɨɛɴɟɤɬ ɢɫɫɥɟɞɨɜɚɧɢɹ ɢ ɢɫɩɨɥɶɡɨɜɚɧɢɹ ɜ ɩɚɬɨɮɢɡɢɨɥɨɝɢɢ…………. 19 1.3.1. Ɋɟɝɭɥɹɬɨɪɵ ȽɋɄ………………………………………………21 1.3.2. Ⱥɥɶɬɟɪɧɚɬɢɜɧɵɟ ɢɫɬɨɱɧɢɤɢ ȽɋɄ……………………………23 1.3.3. Ʉɥɢɧɢɱɟɫɤɚɹ ɷɮɮɟɤɬɢɜɧɨɫɬɶ ɩɭɩɨɜɢɧɧɨɣ ɤɪɨɜɢ…………..25 1.3.4. ɉɪɨɬɟɨɦɢɤɚ ȽɋɄ…………………………………………….. 27 2. ɆȺɌȿɊɂȺɅɕ ɂ ɆȿɌɈȾɕ…………………………………….. 35 2.1. Ʉɥɟɬɨɱɧɵɟ ɥɢɧɢɢ………………………………………………. 35 2.2. Ɇɨɧɨɧɭɤɥɟɚɪɧɵɟ ɤɥɟɬɤɢ………………………………………. 35 2.3. Ƚɟɦɨɩɨɷɬɢɱɟɫɤɢɟ ɫɬɜɨɥɨɜɵɟ ɤɥɟɬɤɢ (ȽɋɄ)……………………35 2.4. ȼɵɞɟɥɟɧɢɟ CD34+ ɫ ɩɨɦɨɳɶɸ ɦɚɝɧɢɬɧɵɯ ɫɮɟɪ………………37 2.5. Ʉɥɟɬɤɢ ɢɡ ɢɧɬɢɦɵ (ɦɟɞɢɢ) ɚɨɪɬɵ………………………………39 2.6. ɉɪɢɝɨɬɨɜɥɟɧɢɟ ɢ ɨɩɬɢɦɢɡɚɰɢɹ ɨɛɪɚɡɰɨɜ ɞɥɹ ɢɫɫɥɟɞɨɜɚɧɢɹ…. 42 2.7. ɉɨɫɥɟɞɨɜɚɬɟɥɶɧɨɫɬɶ (ɚɥɝɨɪɢɬɦ) ɩɪɨɬɟɨɦɧɨɝɨ ɚɧɚɥɢɡɚ…….. 45 2.8. Ɋɚɡɞɟɥɟɧɢɟ ɛɟɥɤɨɜ ɫ ɩɨɦɨɳɶɸ ɞɜɭɦɟɪɧɨɝɨ ɝɟɥɶ-ɷɥɟɤɬɪɨɮɨɪɟɡɚ…47 2.9. Ɉɤɪɚɲɢɜɚɧɢɟ (ɞɟɬɟɤɰɢɹ) ɢ ɜɢɡɭɚɥɢɡɚɰɢɹ ɛɟɥɤɨɜɵɯ ɩɹɬɟɧ…… 48 2.10. Ⱥɧɚɥɢɡ ɢɡɨɛɪɚɠɟɧɢɣ ɢ ɢɞɟɧɬɢɮɢɤɚɰɢɹ ɛɟɥɤɨɜ……………. 48 2.11. Ⱥɧɚɥɢɡ ɞɜɭɦɟɪɧɵɯ ɝɟɥɟɣ……………………………………… 49 2.12. ȼɵɪɟɡɚɧɢɟ ɛɟɥɤɨɜɵɯ ɩɹɬɟɧ……………………………………49 2.13. ɉɟɪɟɜɚɪɢɜɚɧɢɟ ɛɟɥɤɚ ɬɪɢɩɫɢɧɨɦ…………………………… 51 2.14. Ɉɫɨɛɟɧɧɨɫɬɢ ɚɧɚɥɢɡɚ ɤɚɪɞɢɨɩɪɟɩɚɪɚɬɨɜ……………………52 2.15. ɂɞɟɧɬɢɮɢɤɚɰɢɹ ɛɟɥɤɨɜ – MALDI Mass Spec………………. 54 2.16. Ɉɛɴɟɞɢɧɟɧɢɟ ɞɚɧɧɵɯ, ɩɨɥɭɱɟɧɧɵɯ ɧɚ ɪɚɡɧɵɯ ɷɬɚɩɚɯ ɚɧɚɥɢɡɚ... 55 2.17. ɂɞɟɧɬɢɮɢɤɚɰɢɹ ɛɟɥɤɨɜ……………………………………….56 3. ɉɈɅɍɑȿɇɇɕȿ ɊȿɁɍɅɖɌȺɌɕ……………………………….. 59 3.1. ȼɥɢɹɧɢɟ ɩɚɪɚɬɢɪɟɨɢɞɧɨɝɨ ɝɨɪɦɨɧɚ ɧɚ ɨɫɬɟɨɛɥɚɫɬɵ…………59 3.2. Ⱥɧɚɥɢɡ ɩɪɨɬɟɨɦɚ ɝɟɦɨɩɨɷɬɢɱɟɫɤɢɯ ɫɬɜɨɥɨɜɵɯ ɤɥɟɬɨɤ………63 3.2.1. Ɇɨɧɨɧɭɤɥɟɚɪɧɵɟ ɤɥɟɬɤɢ …………………………………… 63 3.2.2. ɉɨɩɭɥɹɰɢɹ CD34+ ɝɟɦɨɩɨɷɬɢɱɟɫɤɢɯ ɫɬɜɨɥɨɜɵɯ ɤɥɟɬɨɤ ….. 74 3.3. ɂɡɭɱɟɧɢɟ ɚɫɫɨɰɢɚɰɢɢ ɩɪɨɬɟɨɦɧɨɝɨ ɩɪɨɮɢɥɹ ɫ ɚɬɟɪɨɫɤɥɟɪɨɡɨɦ………………………………………………....... 82 4. ɈȻɋɍɀȾȿɇɂȿ ɊȿɁɍɅɖɌȺɌɈȼ………………………………. 89 4.1. Ɋɟɚɤɰɢɹ ɩɪɨɬɟɨɦɚ ɨɫɬɟɛɥɚɫɬɨɜ ɧɚ ɩɚɪɚɬɢɪɟɨɢɞɧɵɣ ɝɨɪɦɨɧ.… 89 4.2. ɏɚɪɚɤɬɟɪɢɫɬɢɤɚ ɝɟɦɨɩɨɷɬɢɱɟɫɤɢɯ ɫɬɜɨɥɨɜɵɯ ɤɥɟɬɨɤ………. 92 4.2.1. Ȼɟɥɤɨɜɵɣ ɩɪɨɮɢɥɶ ɦɨɧɨɧɭɤɥɟɚɪɧɵɯ ɤɥɟɬɨɤ……………….92 4.2.2. Ȼɟɥɤɨɜɵɣ ɩɪɨɮɢɥɶ CD34+ ȽɋɄ………………………………96 4.3. ɉɪɨɬɟɨɦɢɤɚ ɚɬɟɪɨɫɤɥɟɪɨɡɚ ɢ ɩɟɪɫɩɟɤɬɢɜɵ ɢɫɩɨɥɶɡɨɜɚɧɢɹ ȽɋɄ ɞɥɹ ɬɟɪɚɩɢɢ ɚɬɟɪɨɫɤɥɟɪɨɡɚ……………………………… 103 ȼɕȼɈȾɕ ……………………………………………………………..111 5 ɋɉɂɋɈɄ ɅɂɌȿɊȺɌɍɊɕ…………………………………………113 ɋɉɂɋɈɄ ɋɈɄɊȺɓȿɇɂɃ………………………………………… 127 ɉɊɂɅɈɀȿɇɂȿ………………………………………………………129 Ɍɚɛɥɢɰɚ 1…………………………………………………………… 129 Ɍɚɛɥɢɰɚ 2…………………………………………………………… 156 Ɍɚɛɥɢɰɚ 3…………………………………………………………… 176 Ɍɚɛɥɢɰɚ 4…………………………………………………………… 190 Ɍɚɛɥɢɰɚ 5…………………………………………………………… 205 Ɍɚɛɥɢɰɚ 6…………………………………………………………… 230 2 ȼȼȿȾȿɇɂȿ Ⱥɤɬɭɚɥɶɧɨɫɬɶ ɬɟɦɵ ɢɫɫɥɟɞɨɜɚɧɢɹ ɨɩɪɟɞɟɥɟɧɚ, ɜɨ-ɩɟɪɜɵɯ, ɬɟɦ, ɱɬɨ ɜ ɦɢɪɟ ɧɚɛɥɸɞɚɟɬɫɹ ɨɝɪɨɦɧɵɣ ɢɧɬɟɪɟɫ ɤ ɩɪɨɬɟɨɦɢɤɟ ɫɨ ɫɬɨɪɨɧɵ ɛɢɨɦɟɞɢɰɢɧɵ ɤɚɤ ɞɥɹ ɪɚɧɧɟɝɨ ɨɛɧɚɪɭɠɟɧɢɹ ɢ ɦɨɧɢɬɨɪɢɧɝɚ ɛɨɥɟɡɧɟɣ, ɬɚɤ ɢ ɞɥɹ ɪɚɡɪɚɛɨɬɤɢ ɛɨɥɟɟ ɷɮɮɟɤɬɢɜɧɵɯ ɦɟɬɨɞɨɜ ɥɟɱɟɧɢɹ ɧɚ ɨɫɧɨɜɟ ɥɭɱɲɟɝɨ ɩɨɧɢɦɚɧɢɹ ɩɚɬɨɝɟɧɟɡɚ. ȼ ɩɨɫɥɟɞɧɢɟ ɝɨɞɵ ɬɟɯɧɨɥɨɝɢɢ ɞɥɹ ɢɞɟɧɬɢɮɢɤɚɰɢɢ ɩɪɨɬɟɨɦɚ ɡɧɚɱɢɬɟɥɶɧɨ ɭɫɨɜɟɪɲɟɧɫɬɜɨɜɚɥɢɫɶ ɛɥɚɝɨɞɚɪɹ ɛɨɥɶɲɟɣ ɱɭɜɫɬɜɢɬɟɥɶɧɨɫɬɢ ɢ ɫɩɟɰɢɮɢɱɧɨɫɬɢ ɚɧɚɥɢɬɢɱɟɫɤɢɯ ɦɟɬɨɞɨɜ, ɢɫɩɨɥɶɡɭɸɳɢɯɫɹ ɜ ɧɢɯ. Ʉɪɨɦɟ ɬɨɝɨ, ɤɨɦɩɶɸɬɟɪɧɵɟ ɬɟɯɧɨɥɨɝɢɢ, ɩɪɢɦɟɧɹɟɦɵɟ ɞɥɹ ɚɧɚɥɢɡɚ ɩɪɨɬɟɨɦɚ, ɫɬɚɥɢ ɛɨɥɟɟ ɦɨɳɧɵɦɢ, ɩɨɹɜɢɥɢɫɶ ɛɢɨɢɧɮɨɪɦɚɬɢɱɟɫɤɢɟ ɢɧɫɬɪɭɦɟɧɬɵ, ɛɥɚɝɨɞɚɪɹ ɤɨɬɨɪɵɦ ɫɬɚɥɨ ɜɨɡɦɨɠɧɵɦ ɢɡɜɥɟɱɟɧɢɟ ɦɚɤɫɢɦɚɥɶɧɨɝɨ ɤɨɥɢɱɟɫɬɜɚ ɢɧɮɨɪɦɚɰɢɢ ɢɡ ɢɫɫɥɟɞɭɟɦɵɯ ɨɛɪɚɡɰɨɜ. Ⱦɚɧɧɵɟ ɬɟɯɧɨɥɨɝɢɢ ɩɨɡɜɨɥɹɸɬ ɜɵɛɪɚɬɶ ɛɟɥɤɨɜɵɟ ɛɢɨɦɚɪɤɟɪɵ, ɚɫɫɨɰɢɢɪɨɜɚɧɧɵɟ ɫ ɡɚɛɨɥɟɜɚɧɢɹɦɢ. ȼɨ-ɜɬɨɪɵɯ, ɩɪɨɬɟɨɦɢɤɚ ɩɨɡɜɨɥɹɟɬ ɩɪɨɜɟɫɬɢ ɬɳɚɬɟɥɶɧɵɣ ɚɧɚɥɢɡ ɛɟɥɤɨɜ ɜ ɨɛɥɚɫɬɢ ɚɬɟɪɨɫɤɥɟɪɨɬɢɱɟɫɤɨɣ ɫɨɫɭɞɢɫɬɨɣ ɬɤɚɧɢ ɢ ɨɛɧɚɪɭɠɢɬɶ ɜɢɞɵ ɛɟɥɤɨɜ, ɤɨɬɨɪɵɟ ɭɱɚɫɬɜɭɸɬ ɜ ɫɨɫɭɞɢɫɬɨɦ ɪɟɦɨɞɟɥɢɪɨɜɚɧɢɢ ɢ ɚɬɟɪɨɝɟɧɟɡɟ. ɂɞɟɧɬɢɮɢɤɚɰɢɹ ɱɟɥɨɜɟɱɟɫɤɨɝɨ ɚɬɟɪɨɫɤɥɟɪɨɬɢɱɟɫɤɨɝɨ ɩɪɨɬɟɨɦɚ ɛɭɞɟɬ ɫɥɭɠɢɬɶ ɮɭɧɞɚɦɟɧɬɨɦ ɞɥɹ ɞɚɥɶɧɟɣɲɢɯ ɢɫɫɥɟɞɨɜɚɧɢɣ, ɩɨɦɨɝɚɹ ɩɨɫɬɪɨɢɬɶ ɢ ɩɪɨɜɟɪɢɬɶ ɧɨɜɵɟ ɝɢɩɨɬɟɡɵ. ȼ-ɬɪɟɬɶɢɯ, ɧɟɞɚɜɧɢɟ ɤɥɢɧɢɱɟɫɤɢɟ ɢɫɫɥɟɞɨɜɚɧɢɹ ɩɨɤɚɡɵɜɚɸɬ, ɱɬɨ ɧɟɞɢɮɮɟɪɟɧɰɢɪɨɜɚɧɧɵɟ ɤɥɟɬɤɢ, ɰɢɪɤɭɥɢɪɭɸɳɢɟ ɜ ɤɪɨɜɨɬɨɤɟ, ɢɦɟɸɬ ɨɝɪɨɦɧɵɣ ɩɨɬɟɧɰɢɚɥ ɞɥɹ ɪɟɝɟɧɟɪɚɰɢɢ ɫɨɫɭɞɢɫɬɨɣ ɬɤɚɧɢ. Ɉɧɢ ɩɚɬɪɭɥɢɪɭɸɬ ɨɪɝɚɧɢɡɦ ɢ ɫɬɟɤɚɸɬɫɹ ɤ ɦɟɫɬɭ, ɝɞɟ ɨɛɧɚɪɭɠɢɜɚɸɬ ɩɨɜɪɟɠɞɟɧɢɟ ɫɨɫɭɞɚ. ɉɨɹɜɥɹɸɬɫɹ ɢ ɧɨɜɵɟ ɞɚɧɧɵɟ ɨɛ ɭɱɚɫɬɢɢ ɫɬɜɨɥɨɜɵɯ ɤɥɟɬɨɤ ɤɚɤ ɝɟɦɨɩɨɷɬɢɱɟɫɤɨɣ, ɬɚɤ ɢ ɫɬɪɨɦɚɥɶɧɨɣ ɥɢɧɢɣ ɞɢɮɮɟɪɟɧɰɢɪɨɜɤɢ, ɜ ɚɬɟɪɨɝɟɧɟɡɟ. ɗɬɢ ɞɚɧɧɵɟ ɩɨɡɜɨɥɢɥɢ ɩɪɟɞɩɨɥɨɠɢɬɶ, ɱɬɨ ɜɚɠɧɵɦ ɦɨ3 ɦɟɧɬɨɦ ɜ ɪɚɡɜɢɬɢɢ ɚɬɟɪɨɫɤɥɟɪɨɡɚ ɹɜɥɹɟɬɫɹ ɩɪɨɧɢɤɧɨɜɟɧɢɟ ɤɨɥɨɧɢɟɨɛɪɚɡɭɸɳɢɯ ɫɬɜɨɥɨɜɵɯ ɤɥɟɬɨɤ ɜ ɢɧɬɢɦɭ ɜ ɦɟɫɬɚɯ ɤɨɧɰɟɧɬɪɚɰɢɢ ɥɢɩɢɞɨɜ. ɉɪɨɬɟɨɦ ɛɨɥɶɲɢɧɫɬɜɚ ɬɚɤɢɯ ɤɥɟɬɨɤ ɤ ɧɚɫɬɨɹɳɟɦɭ ɜɪɟɦɟɧɢ ɢɡɭɱɟɧ ɧɟɞɨɫɬɚɬɨɱɧɨ ɢ ɦɚɥɨɢɡɜɟɫɬɧɨɣ ɨɫɬɚɟɬɫɹ ɟɝɨ ɫɜɹɡɶ ɫ ɩɚɬɨɥɨɝɢɱɟɫɤɢɦɢ ɫɨɫɬɨɹɧɢɹɦɢ ɫɨɫɭɞɨɜ. ȼɢɞɢɦɨ, ɩɟɪɫɩɟɤɬɢɜɟɧ ɢ ɩɨɢɫɤ ɩɨɞɯɨɞɨɜ ɤ ɫɬɢɦɭɥɹɰɢɢ ɪɟɝɟɧɟɪɚɬɢɜɧɨ-ɢɧɞɭɤɰɢɨɧɧɵɯ ɫɜɨɣɫɬɜ ɝɟɦɨɩɨɷɬɢɱɟɫɤɢɯ ɫɬɜɨɥɨɜɵɯ ɤɥɟɬɨɤ (ȽɋɄ), ɜɨɡɪɚɫɬɚɟɬ ɢɧɬɟɪɟɫ ɤ ɩɨɬɟɧɰɢɚɥɶɧɨɦɭ ɢɫɩɨɥɶɡɨɜɚɧɢɸ ɩɭɩɨɜɢɧɧɨɣ ɤɪɨɜɢ ɜ ɤɚɱɟɫɬɜɟ ɢɫɬɨɱɧɢɤɚ ɫɬɜɨɥɨɜɵɯ ɤɥɟɬɨɤ ɞɥɹ ɥɟɱɟɧɢɹ ɪɹɞɚ ɡɚɛɨɥɟɜɚɧɢɣ. ȼ ɷɬɨɣ ɫɜɹɡɢ ɰɟɥɶɸ ɢɫɫɥɟɞɨɜɚɧɢɹ ɫɬɚɥɢ ɤɚɤ ɪɚɫɲɢɮɪɨɜɤɚ, ɧɚ ɨɫɧɨɜɟ ɭɫɨɜɟɪɲɟɧɫɬɜɨɜɚɧɧɨɝɨ ɩɪɨɬɟɨɦɧɨɝɨ ɚɧɚɥɢɡɚ, ɛɟɥɤɨɜɵɯ ɩɪɨɮɢɥɟɣ ȽɋɄ ɢɡ ɩɭɩɨɜɢɧɧɨɣ ɤɪɨɜɢ, ɬɚɤ ɢ ɜɵɹɜɥɟɧɢɟ ɚɫɫɨɰɢɚɰɢɢ ɦɟɠɞɭ ɚɬɟɪɨɫɤɥɟɪɨɬɢɱɟɫɤɢɦɢ ɩɨɪɚɠɟɧɢɹɦɢ ɢ ɩɪɨɬɟɨɦɧɵɦɢ ɩɪɨɮɢɥɹɦɢ ɢɧɬɢɦɵ ɢ ɦɟɞɢɢ ɚɨɪɬɵ ɱɟɥɨɜɟɤɚ ɞɥɹ ɩɨɧɢɦɚɧɢɹ ɩɨɬɟɧɰɢɚɥɶɧɵɯ ɜɨɡɦɨɠɧɨɫɬɟɣ ɢɫɩɨɥɶɡɨɜɚɧɢɹ ȽɋɄ ɜ ɬɟɪɚɩɢɢ ɫɨɫɭɞɢɫɬɵɯ ɩɚɬɨɥɨɝɢɣ. ȼ ɫɨɨɬɜɟɬɫɬɜɢɢ ɫ ɞɚɧɧɨɣ ɰɟɥɶɸ ɜ ɪɚɛɨɬɟ ɪɟɲɚɸɬɫɹ ɫɥɟɞɭɸɳɢɟ ɡɚɞɚɱɢ: 1. Ɉɩɬɢɦɢɡɢɪɨɜɚɬɶ ɚɥɝɨɪɢɬɦ ɩɪɨɬɟɨɦɧɨɝɨ ɚɧɚɥɢɡɚ, ɬɨ ɟɫɬɶ ɫɨɡɞɚɬɶ ɟɞɢɧɭɸ ɫɯɟɦɭ ɢɫɫɥɟɞɨɜɚɧɢɹ ɛɟɥɤɨɜɵɯ ɩɪɨɮɢɥɟɣ, ɤɨɬɨɪɚɹ ɭɩɪɨɳɚɥɚ ɛɵ ɫɪɚɜɧɟɧɢɟ ɞɚɧɧɵɯ, ɩɨɥɭɱɟɧɧɵɯ ɧɚ ɬɚɤɢɯ ɪɚɡɧɵɯ ɨɛɴɟɤɬɚɯ, ɤɚɤ ɨɫɬɟɨɛɥɚɫɬɵ, ɦɨɧɨɧɭɤɥɟɚɪɧɵɟ ɤɥɟɬɤɢ (ɆɇɄ), CD34+ ȽɋɄ ɢ ɢɧɬɢɦɨ-ɦɟɞɢɚɥɶɧɵɣ ɫɥɨɣ ɚɨɪɬɵ ɱɟɥɨɜɟɤɚ. 2. ɂɡɭɱɢɬɶ ɫ ɩɨɦɨɳɶɸ ɩɪɨɬɟɨɦɢɤɢ ɩɨɜɟɞɟɧɢɟ ɛɟɥɤɨɜ ɨɫɬɟɨɛɥɚɫɬɨɜ, ɹɜɥɹɸɳɢɯɫɹ ɜɚɠɧɵɦ ɤɨɦɩɨɧɟɧɬɨɦ ɧɢɲɢ ȽɋɄ ɢ ɢɡɦɟɧɹɸɳɢɯɫɹ ɩɨɞ ɞɟɣɫɬɜɢɟɦ ɩɚɪɚɬɢɪɟɨɢɞɧɨɝɨ ɝɨɪɦɨɧɚ. 3. ɉɪɨɜɟɫɬɢ ɢɞɟɧɬɢɮɢɤɚɰɢɸ ɛɟɥɤɨɜ, ɩɪɢɫɭɬɫɬɜɭɸɳɢɯ ɜ ɆɇɄ, CD34+ ȽɋɄ, ɚ ɬɚɤɠɟ ɧɨɪɦɚɥɶɧɵɯ ɢ ɚɬɟɪɨɫɤɥɟɪɨɬɢɱɟɫɤɢɯ ɬɤɚɧɹɯ ɚɨɪɬɵ. 4 4. ɋɪɚɜɧɢɬɶ ɩɪɨɬɟɨɦɧɵɟ ɩɪɨɮɢɥɢ ȽɋɄ ɢɡ ɩɭɩɨɜɢɧɧɨɣ ɤɪɨɜɢ, ɢɧɬɢɦɵ ɢ ɦɟɞɢɢ ɫɨɫɭɞɨɜ ɜ ɩɪɨɰɟɫɫɟ ɚɬɟɪɨɝɟɧɟɡɚ. ȼɵɹɜɢɬɶ ɛɟɥɤɢ, ɭɪɨɜɧɢ ɤɨɬɨɪɵɯ ɢɡɦɟɧɹɸɬɫɹ ɩɪɢ ɪɚɡɜɢɬɢɢ ɚɬɟɪɨɫɤɥɟɪɨɬɢɱɟɫɤɨɝɨ ɩɨɪɚɠɟɧɢɹ ɜ ɢɧɬɢɦɨ-ɦɟɞɢɚɥɶɧɨɦ ɫɥɨɟ ɚɨɪɬɵ ɱɟɥɨɜɟɤɚ. Ɉɛɴɟɤɬɚɦɢ ɢɫɫɥɟɞɨɜɚɧɢɹ ɛɵɥɢ ɢɡɛɪɚɧɵ ɝɟɦɨɩɨɷɬɢɱɟɫɤɢɟ ɫɬɜɨɥɨɜɵɟ ɤɥɟɬɤɢ, ɜ ɨɫɧɨɜɧɨɦ ɷɬɨ ɛɵɥɢ ɆɇɄ, ɩɨɩɭɥɹɰɢɹ ɤɥɟɬɨɤ CD34+ȽɋɄ, ɨɱɢɳɟɧɧɵɯ ɢ ɜɵɞɟɥɟɧɧɵɯ ɢɡ ɨɛɪɚɡɰɨɜ ɩɭɩɨɜɢɧɧɨɣ ɤɪɨɜɢ, ɨɫɬɟɨɛɥɚɫɬɵ, ɚ ɬɚɤɠɟ ɛɟɥɤɢ ɢɡ ɢɧɬɢɦɵ ɚɨɪɬɵ ɱɟɥɨɜɟɤɚ ɢ ɛɟɥɤɢ ɢɡ ɦɟɞɢɢ ɭɱɚɫɬɤɨɜ ɚɨɪɬɵ ɱɟɥɨɜɟɤɚ ɤɚɤ ɧɟ ɩɨɪɚɠɟɧɧɵɯ ɚɬɟɪɨɫɤɥɟɪɨɡɨɦ, ɬɚɤ ɢ ɫɨɨɬɜɟɬɫɬɜɭɸɳɢɯ ɪɚɡɥɢɱɧɵɦ ɜɢɞɚɦ ɚɬɟɪɨɫɤɥɟɪɨɬɢɱɟɫɤɢɯ ɩɨɪɚɠɟɧɢɣ. ɇɚɭɱɧɚɹ ɧɨɜɢɡɧɚ ɨɛɴɹɫɧɹɟɬɫɹ ɬɟɦ, ɱɬɨ ɭɬɨɱɧɟɧɵ ɞɚɧɧɵɟ ɨ ɛɟɥɤɚɯ, ɜɵɞɟɥɟɧɧɵɯ ɢɡ ɚɬɟɪɨɫɤɥɟɪɨɬɢɱɟɫɤɢɯ ɛɥɹɲɟɤ ɢ ɩɪɟɬɟɪɩɟɜɚɸɳɢɯ ɢɡɦɟɧɟɧɢɟ ɜ ɚɪɬɟɪɢɚɥɶɧɵɯ ɢɧɬɢɦɟ ɢ ɦɟɞɢɢ ɩɪɢ ɪɚɡɜɢɬɢɢ ɚɬɟɪɨɫɤɥɟɪɨɬɢɱɟɫɤɢɯ ɩɨɪɚɠɟɧɢɣ. ɂɞɟɧɬɢɮɢɰɢɪɨɜɚɧɵ ɦɧɨɝɢɟ ɛɟɥɤɢ ȽɋɄ ɢɡ ɩɭɩɨɜɢɧɧɨɣ ɤɪɨɜɢ ɫ ɭɱɟɬɨɦ ɢɯ ɜɧɭɬɪɢɤɥɟɬɨɱɧɨɣ ɥɨɤɚɥɢɡɚɰɢɢ, ɚ ɬɚɤɠɟ ɩɪɨɬɟɨɦ ɨɫɬɟɨɛɥɚɫɬɨɜ ɜ ɞɢɧɚɦɢɤɟ. ɉɨɷɬɨɦɭ ɩɨɥɭɱɟɧɧɵɟ ɧɚɦɢ ɪɟɡɭɥɶɬɚɬɵ ɢɦɟɸɬ ɜɵɫɨɤɭɸ ɫɬɟɩɟɧɶ ɧɨɜɢɡɧɵ. ɂɫɫɥɟɞɨɜɚɧɢɟ ɜɤɥɸɱɚɟɬ ɪɚɡɪɚɛɨɬɤɭ ɨɪɢɝɢɧɚɥɶɧɨɝɨ ɦɟɬɨɞɢɱɟɫɤɨɝɨ ɩɨɞɯɨɞɚ ɤ ɜɵɹɜɥɟɧɢɸ ɛɟɥɤɨɜɵɯ ɩɪɨɮɢɥɟɣ ȽɋɄ, ɚɪɬɟɪɢɚɥɶɧɨɣ ɢɧɬɢɦɵ ɢ ɦɟɞɢɢ ɧɚ ɪɚɧɟɟ ɧɟɞɨɫɬɢɠɢɦɨɦ ɭɪɨɜɧɟ, ɩɨɡɜɨɥɹɸɳɟɦ ɥɭɱɲɟ ɩɨɧɹɬɶ ɢɯ ɫɥɨɠɧɭɸ ɩɪɢɪɨɞɭ. Ɍɟɨɪɟɬɢɱɟɫɤɚɹ ɢ ɩɪɚɤɬɢɱɟɫɤɚɹ ɡɧɚɱɢɦɨɫɬɶ ɪɚɛɨɬɵ ɜɵɪɚɠɚɟɬɫɹ ɜ ɫɨɡɞɚɧɢɢ ɧɚɭɱɧɨ-ɬɟɯɧɢɱɟɫɤɨɝɨ ɡɚɞɟɥɚ, ɨɬɤɪɵɜɚɸɳɟɝɨ ɩɨɬɟɧɰɢɚɥɶɧɵɟ ɜɨɡɦɨɠɧɨɫɬɢ ɢɫɩɨɥɶɡɨɜɚɧɢɹ ȽɋɄ ɜ ɬɟɪɚɩɢɢ ɚɬɟɪɨɫɤɥɟɪɨɡɚ. Ȼɟɥɤɢ, ɢɡɦɟɧɟɧɢɟ ɫɨɞɟɪɠɚɧɢɹ ɤɨɬɨɪɵɯ ɨɛɧɚɪɭɠɟɧɨ ɩɪɢ ɪɚɡɜɢɬɢɢ ɩɚɬɨɥɨɝɢɢ, ɦɨɝɭɬ ɫɨɩɨɫɬɚɜɥɹɬɶɫɹ ɫ ɛɟɥɤɚɦɢ ȽɋɄ ɢ ɨɫɬɟɨɛɥɚɫɬɨɜ, ɚ ɬɚɤɠɟ ɪɚɫɫɦɚɬɪɢɜɚɬɶɫɹ ɤɚɤ ɛɢɨɦɚɪɤɟɪɵ ɞɥɹ ɞɢɚɝɧɨɫɬɢɤɢ ɩɪɟɞɪɚɫ- 5 ɩɨɥɨɠɟɧɧɨɫɬɢ ɤ ɚɬɟɪɨɫɤɥɟɪɨɡɭ, ɱɬɨ ɫɩɨɫɨɛɫɬɜɭɟɬ ɩɟɪɟɯɨɞɭ ɤ ɩɟɪɫɨɧɚɥɢɡɢɪɨɜɚɧɧɨɣ ɦɟɞɢɰɢɧɟ. ɍɫɨɜɟɪɲɟɧɫɬɜɨɜɚɧɧɵɣ ɦɟɬɨɞ ɩɨɞɝɨɬɨɜɤɢ ɫɬɜɨɥɨɜɵɯ ɤɥɟɬɨɤ ɤ ɚɜɬɨɦɚɬɢɡɢɪɨɜɚɧɧɨɦɭ ɩɪɨɬɟɨɦɧɨɦɭ ɚɧɚɥɢɡɭ ɦɨɠɟɬ ɢɫɩɨɥɶɡɨɜɚɬɶɫɹ ɜ ɤɥɢɧɢɤɚɯ ɫɨɨɬɜɟɬɫɬɜɭɸɳɟɝɨ ɩɪɨɮɢɥɹ. Ɉɫɧɨɜɧɵɟ ɧɚɭɱɧɵɟ ɪɟɡɭɥɶɬɚɬɵ. 1. ɍɫɨɜɟɪɲɟɧɫɬɜɨɜɚɧɧɵɣ ɦɟɬɨɞ – ɤɨɦɛɢɧɚɰɢɹ 2D ɷɥɟɤɬɪɨɮɨɪɟɡɚ ɫ ɮɪɚɤɰɢɨɧɢɪɨɜɚɧɢɟɦ ɤɥɟɬɨɱɧɵɯ ɨɪɝɚɧɟɥɥ, ɩɨɡɜɨɥɹɸɳɢɣ ɧɟ ɬɨɥɶɤɨ ɩɪɨɜɟɫɬɢ ɩɪɨɬɟɨɦɧɵɣ ɚɧɚɥɢɡ ɤɥɟɬɨɤ, ɧɨ ɢ ɩɨɥɭɱɢɬɶ ɢɧɮɨɪɦɚɰɢɸ ɨ ɜɧɭɬɪɢɤɥɟɬɨɱɧɨɣ ɥɨɤɚɥɢɡɚɰɢɢ ɢɞɟɧɬɢɮɢɰɢɪɨɜɚɧɧɵɯ ɛɟɥɤɨɜ. Ɇɟɬɨɞ ɨɬɥɢɱɚɟɬɫɹ ɜɨɫɩɪɨɢɡɜɨɞɢɦɨɫɬɶɸ ɢ ɜɨɡɦɨɠɧɨɫɬɶɸ ɤɨɥɢɱɟɫɬɜɟɧɧɨɣ ɨɰɟɧɤɢ ɪɟɡɭɥɶɬɚɬɨɜ, ɛɨɥɶɲɢɧɫɬɜɨ ɟɝɨ ɫɬɚɞɢɣ ɚɜɬɨɦɚɬɢɡɢɪɨɜɚɧɨ. 2. ȼ ɷɤɫɩɟɪɢɦɟɧɬɚɯ ɧɚ ɨɫɬɟɨɛɥɚɫɬɚɯ ɩɨɞɬɜɟɪɠɞɟɧɨ, ɱɬɨ ɚɥɝɨɪɢɬɦ ɩɪɨɬɟɨɦɧɨɝɨ ɚɧɚɥɢɡɚ ɨɩɬɢɦɢɡɢɪɨɜɚɧ. Ɉɧ ɦɨɠɟɬ ɩɪɢɦɟɧɹɬɶɫɹ ɞɥɹ ɧɚɛɥɸɞɟɧɢɹ ɡɚ ɞɢɧɚɦɢɤɨɣ ɢɡɦɟɧɟɧɢɹ ɛɟɥɤɨɜ ɜ ɨɬɜɟɬ ɧɚ ɜɧɟɲɧɢɟ ɜɨɡɞɟɣɫɬɜɢɹ, ɜ ɬɨɦ ɱɢɫɥɟ ɧɚ ɜɥɢɹɧɢɟ ɮɚɤɬɨɪɨɜ ɤɨɫɬɧɨɝɨ ɦɨɡɝɚ, ɬ.ɟ. ɝɟɦɨɩɨɷɬɢɱɟɫɤɨɣ ɤɥɟɬɨɱɧɨɣ ɧɢɲɢ ɋɄ. ɗɬɨ, ɜ ɫɜɨɸ ɨɱɟɪɟɞɶ, ɞɚɫɬ ɜɨɡɦɨɠɧɨɫɬɶ ɩɪɨɜɨɞɢɬɶ ɷɤɫɩɚɧɫɢɸ ȽɋɄ ɜ ɭɫɥɨɜɢɹɯ in vitro. 3. Ɉɩɢɫɚɧ ɩɪɨɬɟɨɦɧɵɣ ɩɪɨɮɢɥɶ ɆɇɄ ɢ CD34+ȽɋɄ ɫ ɜɵɫɨɤɢɦ ɪɚɡɪɟɲɟɧɢɟɦ, ɬɨ ɟɫɬɶ ɫɞɟɥɚɧ ɨɱɟɪɟɞɧɨɣ ɲɚɝ ɜ ɩɨɫɬɪɨɟɧɢɢ ɝɥɨɛɚɥɶɧɨɝɨ ɩɪɨɬɟɨɦɧɨɝɨ ɩɪɨɮɢɥɹ ɦɨɧɨɧɭɤɥɟɚɪɧɵɯ ɤɥɟɬɨɤ ɢ CD34+ ȽɋɄ. 4. ɉɪɨɜɟɞɟɧ ɞɜɭɦɟɪɧɵɣ ɷɥɟɤɬɪɨɮɨɪɟɡ ɛɟɥɤɨɜ ɢɡ ɢɧɬɢɦɵ ɢ ɦɟɞɢɢ ɚɨɪɬɵ, ɩɨɥɭɱɟɧɵ ɩɪɨɬɟɨɦɧɵɟ ɩɪɨɮɢɥɢ ɪɚɡɥɢɱɧɵɯ ɜɢɞɨɜ ɚɬɟɪɨɫɤɥɟɪɨɬɢɱɟɫɤɢɯ ɩɨɪɚɠɟɧɢɣ (ɠɢɪɨɜɚɹ ɢɧɮɢɥɶɬɪɚɰɢɹ, ɠɢɪɨɜɚɹ ɩɨɥɨɫɚ, ɥɢɩɨɮɢɛɪɨɡɧɚɹ ɛɥɹɲɤɚ, ɮɢɛɪɨɡɧɚɹ ɛɥɹɲɤɚ) ɜ ɫɪɚɜɧɟɧɢɢ ɫ ɧɟɩɨɪɚɠɟɧɧɵɦɢ ɚɬɟɪɨɫɤɥɟɪɨɡɨɦ ɭɱɚɫɬɤɚɦɢ. Ɉɛɧɚɪɭɠɟɧɵ ɛɟɥɤɨɜɵɟ ɩɹɬɧɚ, ɩɪɨɹɜɥɹɸɳɢɟ ɪɚɡɥɢɱɢɹ ɩɪɢ ɫɪɚɜɧɟɧɢɢ ɩɪɨɬɟɨɦɧɵɯ ɩɪɨɮɢɥɟɣ, ɩɨɞɥɟɠɚɳɢɯ ɩɨɞ 6 ɧɟɩɨɪɚɠɟɧɧɵɦɢ ɭɱɚɫɬɤɚɦɢ ɢɧɬɢɦɵ ɢ ɦɟɞɢɢ ɢ ɩɨɞ ɥɢɩɨɮɢɛɪɨɡɧɵɦɢ ɛɥɹɲɤɚɦɢ. ɉɪɟɞɩɪɢɧɹɬɚ ɩɨɩɵɬɤɚ ɢɞɟɧɬɢɮɢɤɚɰɢɢ ɷɬɢɯ ɛɟɥɤɨɜ ɫ ɩɨɦɨɳɶɸ MALDI-TOF ɦɚɫɫ-ɫɩɟɤɬɪɨɦɟɬɪɢɢ. 5. ɉɨɞɬɜɟɪɠɞɟɧɚ ɪɨɥɶ ɜ ɮɨɪɦɢɪɨɜɚɧɢɢ ɚɬɟɪɨɫɤɥɟɪɨɬɢɱɟɫɤɨɣ ɛɥɹɲɤɢ ɬɚɤɢɯ ɧɢɡɤɨɦɨɥɟɤɭɥɹɪɧɵɯ ɛɟɥɤɨɜ, ɤɚɤ ɚɧɧɟɤɫɢɧɵ ɢ ɛɟɥɤɢ ɬɟɩɥɨɜɨɝɨ ɲɨɤɚ. 7 8 1. ɉɊɈɌȿɈɆɂɄȺ ɂ ɉɈɌȿɇɐɂȺɅ ɋɌȼɈɅɈȼɕɏ ɄɅȿɌɈɄ ȾɅə ɌȿɊȺɉɂɂ ȺɌȿɊɈɋɄɅȿɊɈɁȺ 1.1. ɉɪɨɬɟɨɦɢɤɚ ɤɚɤ ɢɧɫɬɪɭɦɟɧɬ ɢɡɭɱɟɧɢɹ ɤɥɟɬɨɤ ȼ ɩɨɫɥɟɞɧɢɟ ɝɨɞɵ ɬɟɯɧɨɥɨɝɢɢ, ɩɪɢɦɟɧɹɟɦɵɟ ɞɥɹ ɢɫɫɥɟɞɨɜɚɧɢɣ ɩɪɨɬɟɨɦɚ, ɡɧɚɱɢɬɟɥɶɧɨ ɭɫɨɜɟɪɲɟɧɫɬɜɨɜɚɥɢɫɶ ɛɥɚɝɨɞɚɪɹ ɛɨɥɶɲɟɣ ɱɭɜɫɬɜɢɬɟɥɶɧɨɫɬɢ ɢ ɫɩɟɰɢɮɢɱɧɨɫɬɢ ɦɟɬɨɞɨɜ, ɢɫɩɨɥɶɡɭɸɳɢɯɫɹ ɜ ɧɢɯ [27]. Ɍɟɦ ɧɟ ɦɟɧɟɟ, ɞɨ ɫɢɯ ɩɨɪ ɫɭɳɟɫɬɜɟɧɧɭɸ ɩɪɨɛɥɟɦɭ ɩɪɟɞɫɬɚɜɥɹɟɬ ɨɬɫɭɬɫɬɜɢɟ ɟɞɢɧɨɣ ɫɯɟɦɵ ɚɧɚɥɢɡɚ, ɤɨɬɨɪɚɹ ɭɩɪɨɳɚɥɚ ɛɵ ɫɪɚɜɧɟɧɢɟ ɞɚɧɧɵɯ, ɩɨɥɭɱɟɧɧɵɯ ɜ ɪɚɡɧɵɯ ɥɚɛɨɪɚɬɨɪɢɹɯ. ȼ ɷɬɨɣ ɫɜɹɡɢ ɜɪɟɦɹ ɨɬ ɜɪɟɦɟɧɢ ɩɪɟɞɩɪɢɧɢɦɚɸɬɫɹ ɩɨɩɵɬɤɢ ɧɟɤɨɟɣ ɫɬɚɧɞɚɪɬɢɡɚɰɢɢ ɩɪɨɬɟɨɦɢɱɟɫɤɢɯ ɩɪɨɰɟɞɭɪ, ɜ ɬɨɦ ɱɢɫɥɟ ɩɨ ɢɧɢɰɢɚɬɢɜɟ ɦɟɠɞɭɧɚɪɨɞɧɵɯ ɧɚɭɱɧɵɯ ɨɪɝɚɧɢɡɚɰɢɣ (ɜ ɱɚɫɬɧɨɫɬɢ, HUPO) . Ɇɨɠɧɨ ɭɤɚɡɚɬɶ ɧɚ ɜɧɟɞɪɟɧɢɟ, ɧɚɩɪɢɦɟɪ, ɫɬɚɧɞɚɪɬɧɵɯ ɩɪɨɰɟɞɭɪ ɤɨɦɩɶɸɬɟɪɧɨɣ ɨɛɪɚɛɨɬɤɢ ɢɡɨɛɪɚɠɟɧɢɣ ɝɟɥɟɣ (ɜ ɮɨɪɦɚɬɟ .tiff ɮɚɣɥɨɜ), ɱɬɨ ɩɨɡɜɨɥɹɟɬ ɯɪɚɧɢɬɶ ɢɧɮɨɪɦɚɰɢɸ ɫ ɨɞɧɨɬɢɩɧɵɦɢ ɯɚɪɚɤɬɟɪɢɫɬɢɤɚɦɢ. Ɉɞɧɚɤɨ ɦɧɨɝɢɟ ɬɪɭɞɧɨɫɬɢ ɧɚ ɷɬɨɦ ɩɭɬɢ ɨɫɬɚɸɬɫɹ ɧɟɩɪɟɨɞɨɥɟɧɧɵɦɢ ɢ ɞɚɠɟ ɜɨɡɪɚɫɬɚɸɬ ɜ ɫɜɹɡɢ ɫ ɦɨɞɟɪɧɢɡɚɰɢɟɣ ɢ ɞɢɜɟɪɫɢɮɢɤɚɰɢɟɣ ɢɫɩɨɥɶɡɭɟɦɨɝɨ ɪɚɡɧɵɦɢ ɢɫɫɥɟɞɨɜɚɬɟɥɹɦɢ ɨɛɨɪɭɞɨɜɚɧɢɹ. Ɍɢɩɢɱɧɚɹ ɩɨɫɥɟɞɨɜɚɬɟɥɶɧɨɫɬɶ ɨɩɟɪɚɰɢɣ ɩɪɢ ɢɫɫɥɟɞɨɜɚɧɢɹɯ ɜ ɩɪɨɬɟɨɦɢɤɟ ɬɚɤɨɜɚ [12]: − ɨɬɛɨɪ ɨɛɪɚɡɰɚ (ɤɥɟɬɤɢ, ɬɤɚɧɶ, ɛɢɨɥɨɝɢɱɟɫɤɚɹ ɠɢɞɤɨɫɬɶ); − ɩɪɢɝɨɬɨɜɥɟɧɢɟ ɨɛɪɚɡɰɚ, ɥɢɡɢɫ ɤɥɟɬɨɤ, ɷɤɫɬɪɚɤɰɢɹ ɛɟɥɤɨɜ; − ɢɡɨɷɥɟɤɬɪɨɮɨɤɭɫɢɪɨɜɤɚ, ɷɥɟɤɬɪɨɮɨɪɟɡ ɜ 1-ɨɦ ɧɚɩɪɚɜɥɟɧɢɢ; − ɷɥɟɤɬɪɨɮɨɪɟɡ ɜ 2-ɨɦ ɧɚɩɪɚɜɥɟɧɢɢ, ɩɨɥɢɚɤɪɢɥɚɦɢɞɧɵɣ ɝɟɥɶ, ɞɨɞɟɰɢɥɫɭɥɶɮɚɬ ɧɚɬɪɢɹ; − ɩɪɨɹɜɥɟɧɢɟ ɛɟɥɤɨɜɵɯ ɩɹɬɟɧ ɧɚ ɝɟɥɟ; 9 − ɚɧɚɥɢɡ ɞɜɭɦɟɪɧɨɣ ɷɥɟɤɬɪɨɮɨɪɟɝɪɚɦɦɵ (ɤɨɥɢɱɟɫɬɜɨ ɩɹɬɟɧ, ɢɯ ɪɚɡɦɟɪ ɢ ɪɚɫɩɨɥɨɠɟɧɢɟ); − ɜɵɞɟɥɟɧɢɟ ɭɱɚɫɬɤɨɜ ɝɟɥɹ, ɫɨɞɟɪɠɚɳɢɯ ɢɧɞɢɜɢɞɭɚɥɶɧɵɟ ɛɟɥɤɨɜɵɟ ɩɹɬɧɚ; − ɪɚɫɳɟɩɥɟɧɢɟ ɢɧɞɢɜɢɞɭɚɥɶɧɵɯ ɛɟɥɤɨɜ ɬɪɢɩɫɢɧɨɦ ɩɪɹɦɨ ɜ ɝɟɥɟ; − ɦɚɫɫ-ɫɩɟɤɬɪɨɦɟɬɪɢɱɟɫɤɢɣ ɚɧɚɥɢɡ: ɦɚɫɫ-ɮɢɧɝɟɪɩɪɢɧɬɢɧɝ ɩɟɩɬɢɞɨɜ, ɨɩɪɟɞɟɥɟɧɢɟ ɚɦɢɧɨɤɢɫɥɨɬɧɵɯ ɩɨɫɥɟɞɨɜɚɬɟɥɶɧɨɫɬɟɣ ɮɪɚɝɦɟɧɬɨɜ ɢɧɞɢɜɢɞɭɚɥɶɧɵɯ ɛɟɥɤɨɜ, ɢɞɟɧɬɢɮɢɤɚɰɢɹ ɤɚɠɞɨɝɨ ɛɟɥɤɚ ɢ ɢɡɦɟɪɟɧɢɟ ɟɝɨ ɤɨɧɰɟɧɬɪɚɰɢɢ, ɞɨɤɭɦɟɧɬɢɪɨɜɚɧɢɟ, ɨɛɪɚɛɨɬɤɚ ɪɟɡɭɥɶɬɚɬɨɜ. ɂ, ɧɚɤɨɧɟɰ, ɢɧɬɟɪɩɪɟɬɚɰɢɹ ɩɨɥɭɱɟɧɧɵɯ ɞɚɧɧɵɯ ɫ ɩɨɦɨɳɶɸ ɛɢɨɢɧɮɨɪɦɚɬɢɤɢ, ɚɧɚɥɢɡ ɛɚɡ ɞɚɧɧɵɯ, ɜ ɢɬɨɝɟ – ɩɨɥɭɱɟɧɢɟ ɞɢɮɮɟɪɟɧɰɢɚɥɶɧɨɝɨ ɩɪɨɮɢɥɹ ɛɟɥɤɨɜ. Ɂɧɚɱɢɬɟɥɶɧɨɦɭ ɩɪɨɝɪɟɫɫɭ ɜ ɨɛɥɚɫɬɢ ɩɪɨɬɟɨɦɢɤɢ ɫɩɨɫɨɛɫɬɜɨɜɚɥɢ ɭɫɩɟɯɢ ɦɚɫɫ-ɫɩɟɤɬɪɨɦɟɬɪɢɱɟɫɤɨɝɨ ɚɧɚɥɢɡɚ ɩɟɩɬɢɞɨɜ [53]. Ɇɚɫɫɫɩɟɤɬɪɨɦɟɬɪɢɹ ɜɤɥɸɱɚɟɬ ɜ ɫɟɛɹ ɬɪɢ ɨɫɧɨɜɧɵɯ ɤɨɦɩɨɧɟɧɬɚ. ȼɨ-ɩɟɪɜɵɯ, ɜ ɢɨɧɧɨɦ ɢɫɬɨɱɧɢɤɟ ɦɚɫɫ-ɫɩɟɤɬɪɨɦɟɬɪɚ ɢɡ ɨɛɪɚɡɰɚ ɩɨɥɭɱɚɸɬ ɢɨɧɢɡɢɪɨɜɚɧɧɵɟ ɩɟɩɬɢɞɵ ɢɥɢ ɛɟɥɤɢ. ȼɨ-ɜɬɨɪɵɯ, ɪɚɡɞɟɥɟɧɢɟ ɢɨɧɨɜ ɩɟɩɬɢɞɨɜ ɢ ɛɟɥɤɨɜ ɩɪɨɢɫɯɨɞɢɬ ɜ ɚɧɚɥɢɡɚɬɨɪɟ ɦɚɫɫ ɧɚ ɨɫɧɨɜɟ ɢɯ ɜɟɥɢɱɢɧɵ ɨɬɧɨɲɟɧɢɹ ɦɚɫɫɵ ɤ ɡɚɪɹɞɭ (m/z). ȼ-ɬɪɟɬɶɢɯ, ɞɟɬɟɤɬɨɪ ɢɨɧɨɜ (ɜɪɟɦɹɩɪɨɥɟɬɧɵɣ ɦɚɫɫ-ɫɩɟɤɬɪɨɦɟɬɪ) ɪɟɝɢɫɬɪɢɪɭɟɬ ɨɬɞɟɥɶɧɵɟ ɢɨɧɵ, ɫ ɭɤɚɡɚɧɢɟɦ ɡɧɚɱɟɧɢɹ m/z ɢɨɧɚ, ɤɨɥɢɱɟɫɬɜɚ ɢɨɧɨɜ ɢ ɜɪɟɦɟɧɢ ɩɪɨɥɟɬɚ ɢɨɧɨɜ ɨɬ ɢɫɬɨɱɧɢɤɚ ɞɨ ɞɟɬɟɤɬɨɪɚ ɢɨɧɨɜ. ɍɤɚɠɟɦ ɧɚ ɨɫɨɛɟɧɧɨɫɬɢ ɩɪɨɰɟɞɭɪ ɩɪɨɬɟɨɦɧɨɝɨ ɚɧɚɥɢɡɚ. ȿɝɨ ɷɮɮɟɤɬɢɜɧɨɫɬɶ ɦɨɠɧɨ ɩɨɜɵɫɢɬɶ ɡɚ ɫɱɟɬ ɚɜɬɨɦɚɬɢɡɚɰɢɢ ɪɹɞɚ ɫɬɚɞɢɣ, ɱɬɨ ɤ ɬɨɦɭ ɠɟ ɨɛɟɫɩɟɱɢɜɚɟɬ ɛɨɥɟɟ ɜɵɫɨɤɭɸ ɩɪɨɢɡɜɨɞɢɬɟɥɶɧɨɫɬɶ ɩɪɨɰɟɫɫɚ, ɞɚɸɳɭɸ ɜɨɡɦɨɠɧɨɫɬɶ ɢɞɟɧɬɢɮɢɰɢɪɨɜɚɬɶ ɞɨ ɧɟɫɤɨɥɶɤɢɯ ɫɨɬɟɧ ɛɟɥɤɨɜ ɡɚ ɨɞɢɧ ɷɤɫɩɟɪɢɦɟɧɬ. ɇɢɠɟ ɩɪɟɞɫɬɚɜɥɟɧɨ ɤɪɚɬɤɨɟ ɨɩɢɫɚɧɢɟ ɫɬɚɞɢɣ 10 ɷɤɫɩɟɪɢɦɟɧɬɚɥɶɧɨɝɨ ɚɥɝɨɪɢɬɦɚ ɩɪɨɬɟɨɦɧɨɝɨ ɚɧɚɥɢɡɚ. ɒɚɝ 1 – ɩɪɢɝɨɬɨɜɥɟɧɢɟ ɨɛɪɚɡɰɚ (ɩɨɥɭɱɟɧɢɟ ɤɥɟɬɨɤ). Ⱦɥɹ ɛɨɥɶɲɢɧɫɬɜɚ ɩɪɨɬɟɨɦɧɵɯ ɢɫɫɥɟɞɨɜɚɧɢɣ ɢɫɬɨɱɧɢɤ ɞɥɹ ɩɨɥɭɱɟɧɢɹ ɨɛɪɚɡɰɚ ɢɝɪɚɟɬ ɜɚɠɧɟɣɲɭɸ ɪɨɥɶ, ɱɬɨ ɜ ɨɫɨɛɟɧɧɨɫɬɢ ɤɚɫɚɟɬɫɹ ɭɫɥɨɜɢɣ, ɩɪɟɞɲɟɫɬɜɭɸɳɢɯ ɚɧɚɥɢɡɭ, ɢ ɤɨɥɢɱɟɫɬɜɚ ɨɛɪɚɡɰɚ. ɉɪɢ ɪɚɛɨɬɟ ɫ ȽɋɄ ɤɨɥɢɱɟɫɬɜɨ ɦɚɬɟɪɢɚɥɚ ɱɚɫɬɨ ɹɜɥɹɟɬɫɹ ɨɝɪɚɧɢɱɟɧɧɵɦ (1–2 ɦɥɧ. ɤɥɟɬɨɤ ɧɚ ɩɪɨɛɭ ɩɭɩɨɜɢɧɧɨɣ ɤɪɨɜɢ). ɗɬɨ ɨɡɧɚɱɚɟɬ, ɱɬɨ ɤɚɠɞɚɹ ɩɨɫɥɟɞɭɸɳɚɹ ɫɬɚɞɢɹ ɚɧɚɥɢɡɚ ɞɨɥɠɧɚ ɛɵɬɶ ɜɵɫɨɤɨɷɮɮɟɤɬɢɜɧɨɣ, ɱɬɨɛɵ ɧɟ ɫɞɟɥɚɬɶ ɩɪɟɞɲɟɫɬɜɭɸɳɭɸ ɪɚɛɨɬɭ ɧɚɩɪɚɫɧɨɣ. ɒɚɝ 2 – ɥɢɡɢɫ ɤɥɟɬɨɤ (ɩɨɥɭɱɟɧɢɟ ɛɟɥɤɚ). ȼɵɞɟɥɟɧɢɟ ɛɟɥɤɚ ɢɡ ɤɥɟɬɨɤ – ɧɟ ɦɟɧɟɟ ɜɚɠɧɵɣ ɲɚɝ, ɱɟɦ ɩɪɟɞɵɞɭɳɢɣ. Ɏɨɪɦɚ, ɜ ɤɨɬɨɪɨɣ ɜɵɞɟɥɹɸɬɫɹ ɛɟɥɤɢ, ɨɩɪɟɞɟɥɹɟɬ ɞɚɥɶɧɟɣɲɢɣ ɯɨɞ ɚɧɚɥɢɡɚ. Ȼɨɥɟɟ ɬɨɝɨ, ɢɫɩɨɥɶɡɨɜɚɧɢɟ ɧɚ ɷɬɨɦ ɷɬɚɩɟ ɫɭɛɤɥɟɬɨɱɧɨɝɨ ɮɪɚɤɰɢɨɧɢɪɨɜɚɧɢɹ ɩɨɡɜɨɥɹɟɬ ɭɜɟɥɢɱɢɬɶ ɪɚɡɪɟɲɚɸɳɭɸ ɫɩɨɫɨɛɧɨɫɬɶ ɦɟɬɨɞɚ ɢ ɟɝɨ ɢɧɮɨɪɦɚɰɢɨɧɧɵɟ ɜɨɡɦɨɠɧɨɫɬɢ. ɒɚɝ 3 – ɪɚɡɞɟɥɟɧɢɟ ɛɟɥɤɨɜ ɢ ɢɯ ɤɨɥɢɱɟɫɬɜɟɧɧɨɟ ɨɩɪɟɞɟɥɟɧɢɟ. Ȼɟɥɤɢ, ɜɵɞɟɥɟɧɧɵɟ ɢɡ ɤɥɟɬɨɤ, ɞɨɥɠɧɵ ɛɵɬɶ ɪɚɡɞɟɥɟɧɵ ɞɥɹ ɢɯ ɞɚɥɶɧɟɣɲɟɣ ɢɞɟɧɬɢɮɢɤɚɰɢɢ. Ⱦɥɹ ɷɬɨɝɨ ɫɭɳɟɫɬɜɭɟɬ ɰɟɥɵɣ ɪɹɞ ɜɨɡɦɨɠɧɨɫɬɟɣ [52], ɩɪɢɦɟɧɹɟɦɵɯ ɜ ɡɚɜɢɫɢɦɨɫɬɢ ɨɬ ɪɹɞɚ ɮɚɤɬɨɪɨɜ. ɍɫɬɨɹɜɲɟɣɫɹ ɚɥɶɬɟɪɧɚɬɢɜɨɣ ɞɥɹ ɩɪɨɬɟɨɦɢɤɢ ɹɜɥɹɟɬɫɹ ɩɪɨɰɟɞɭɪɚ, ɢɡɜɟɫɬɧɚɹ ɤɚɤ ɞɜɭɦɟɪɧɵɣ ɝɟɥɶ-ɷɥɟɤɬɪɨɮɨɪɟɡ (2D). ɒɚɝ 4 – ɜɢɡɭɚɥɢɡɚɰɢɹ ɢ ɜɵɪɟɡɚɧɢɟ ɛɟɥɤɨɜɵɯ ɩɹɬɟɧ. ɉɨ ɨɤɨɧɱɚɧɢɢ ɷɥɟɤɬɪɨɮɨɪɟɡɚ ɝɟɥɶ ɨɩɭɫɤɚɸɬ ɜ ɛɭɮɟɪ ɞɥɹ ɩɟɪɟɧɨɫɚ. ɉɨɫɥɟ ɪɚɡɞɟɥɟɧɢɹ ɞɜɭɦɟɪɧɵɦ ɷɥɟɤɬɪɨɮɨɪɟɡɨɦ ɢ ɨɤɪɚɲɢɜɚɧɢɹ Ʉɭɦɚɫɫɢ R350, ɤɭɫɨɱɤɢ ɝɟɥɹ ɞɢɚɦɟɬɪɨɦ 1–1,5 ɦɦ, ɫɨɨɬɜɟɬɫɬɜɭɸɳɢɟ ɛɟɥɤɨɜɵɦ ɩɹɬɧɚɦ, ɜɵɪɟɡɚɸɬ. Ɉɤɪɚɲɢɜɚɧɢɟ ɛɟɥɤɨɜɨɝɨ ɝɟɥɹ – ɲɚɝ ɤ ɜɵɪɟɡɚɧɢɸ ɛɟɥɤɨɜɵɯ ɩɹɬɟɧ. Ɉɤɪɚɲɢɜɚɧɢɟ ɛɟɥɤɚ ɩɨɡɜɨɥɹɟɬ ɨɛɧɚɪɭɠɢɬɶ ɢ ɧɢɡɤɨɤɨɧɰɟɧɬɪɢɪɨɜɚɧ11 ɧɵɟ ɛɟɥɤɢ, ɧɨ ɩɪɢ ɷɬɨɦ ɧɟ ɬɪɟɛɭɟɬɫɹ ɛɨɥɶɲɨɣ ɱɭɜɫɬɜɢɬɟɥɶɧɨɫɬɢ, ɬɚɤ ɤɚɤ ɥɢɦɢɬɢɪɭɸɳɢɦ ɮɚɤɬɨɪɨɦ ɹɜɥɹɟɬɫɹ ɜɟɥɢɱɢɧɚ ɤɨɧɰɟɧɬɪɚɰɢɢ, ɧɟɨɛɯɨɞɢɦɚɹ ɞɥɹ ɩɨɫɥɟɞɭɸɳɟɝɨ ɩɨɥɭɱɟɧɢɹ ɛɟɥɤɨɜ ɜ ɤɨɥɢɱɟɫɬɜɟ, ɬɪɟɛɭɟɦɨɦ ɞɥɹ ɢɯ ɢɞɟɧɬɢɮɢɤɚɰɢɢ. Ɉɛɨɪɭɞɨɜɚɧɢɟ, ɢɫɩɨɥɶɡɭɟɦɨɟ ɞɥɹ ɜɢɡɭɚɥɢɡɚɰɢɢ ɛɟɥɤɨɜɵɯ ɩɹɬɟɧ, ɧɟ ɞɨɥɠɧɨ ɜɥɢɹɬɶ ɧɚ ɫɩɨɫɨɛɧɨɫɬɶ ɢɫɫɥɟɞɨɜɚɬɟɥɹ ɢɞɟɧɬɢɮɢɰɢɪɨɜɚɬɶ ɢ ɜɵɞɟɥɹɬɶ ɩɹɬɧɚ ɢɧɞɢɜɢɞɭɚɥɶɧɵɯ ɛɟɥɤɨɜ, ɱɬɨ ɱɚɫɬɨ ɜɫɬɪɟɱɚɟɬɫɹ ɜ ɨɛɪɚɡɰɚɯ ɫ ɧɢɡɤɢɦ ɪɚɡɪɟɲɟɧɢɟɦ. ȼ ɢɞɟɚɥɟ, ɩɪɨɰɟɞɭɪɚ ɜɵɪɟɡɚɧɢɹ ɛɟɥɤɨɜ ɞɨɥɠɧɚ ɛɵɬɶ ɚɜɬɨɦɚɬɢɡɢɪɨɜɚɧɚ ɜ ɢɧɬɟɪɟɫɚɯ ɬɨɱɧɨɫɬɢ ɢ ɷɮɮɟɤɬɢɜɧɨɫɬɢ ɚɧɚɥɢɡɚ. ɒɚɝ 5 – ɩɟɪɟɜɚɪɢɜɚɧɢɟ ɢ ɢɞɟɧɬɢɮɢɤɚɰɢɹ ɛɟɥɤɨɜ. ɉɟɪɟɜɚɪɢɜɚɧɢɟ ɛɟɥɤɨɜɵɯ ɩɹɬɟɧ ɩɨɞ ɞɟɣɫɬɜɢɟɦ ɬɪɢɩɫɢɧɚ, ɤɚɤ ɩɪɚɜɢɥɨ, ɦɧɨɝɨɤɪɚɬɧɚɹ ɩɪɨɰɟɞɭɪɚ, ɤɨɬɨɪɭɸ ɩɪɟɞɩɨɱɬɢɬɟɥɶɧɨ ɚɜɬɨɦɚɬɢɡɢɪɨɜɚɬɶ ɞɥɹ ɫɧɢɠɟɧɢɹ ɜɚɪɢɚɛɟɥɶɧɨɫɬɢ ɨɬ ɩɪɨɛɵ ɤ ɩɪɨɛɟ ɢ ɭɫɬɪɚɧɟɧɢɹ ɞɪɭɝɢɯ ɨɲɢɛɨɤ. Ɍɚɤɠɟ ɩɪɟɞɩɨɱɬɢɬɟɥɶɧɚ ɚɜɬɨɦɚɬɢɡɚɰɢɹ ɢ ɞɥɹ ɩɪɨɰɟɞɭɪɵ ɧɚɧɟɫɟɧɢɹ ɩɟɪɟɜɚɪɟɧɧɨɝɨ ɨɛɪɚɡɰɚ ɧɚ ɩɥɚɬɵ ɞɥɹ MALDIɢɞɟɧɬɢɮɢɤɚɰɢɢ. ɉɪɨɞɭɤɬɵ ɝɢɞɪɨɥɢɡɚ ɫɦɟɲɢɜɚɸɬ ɩɪɹɦɨ ɧɚ ɩɥɚɫɬɢɧɤɟ ɞɥɹ ɦɚɫɫ-ɫɩɟɤɬɪɨɫɤɨɩɢɢ ɫ ɦɚɬɪɢɰɟɣ (ɚɥɶɮɚ-ɰɢɚɧɨ-4-ɝɢɞɪɨɨɤɫɢ- ɤɨɪɢɱɧɚɹ ɤɢɫɥɨɬɚ, ɧɚɫɵɳɟɧɧɵɣ ɪɚɫɬɜɨɪ ɜ ɚɰɟɬɨɧɟ). ɉɪɢɫɜɨɟɧɢɟ ID (ɢɞɟɧɬɢɮɢɤɚɰɢɨɧɧɨɝɨ ɧɨɦɟɪɚ) ɛɟɥɤɭ ɞɚɧɧɨɝɨ ɨɛɪɚɡɰɚ – ɩɨɫɥɟɞɧɢɣ ɲɚɝ ɚɧɚɥɢɡɚ, ɫ ɭɱɟɬɨɦ ɭɫɬɚɧɨɜɥɟɧɧɨɝɨ ɤɪɢɬɟɪɢɹ ɧɚɞɟɠɧɨɫɬɢ ɞɥɹ ɜɫɟɯ ɩɪɨɰɟɞɭɪ. ȼ ɷɬɨɦ ɫɥɭɱɚɟ ɨɛɟɫɩɟɱɢɜɚɟɬɫɹ ɜɨɫɩɪɨɢɡɜɨɞɢɦɨɫɬɶ ɪɟɡɭɥɶɬɚɬɨɜ ɤɚɤ ɜɧɭɬɪɢ-, ɬɚɤ ɢ ɦɟɠɥɚɛɨɪɚɬɨɪɧɵɯ ɷɤɫɩɟɪɢɦɟɧɬɨɜ. ɇɚɥɢɱɢɟ ɜ ɨɩɢɫɚɧɧɨɦ ɷɤɫɩɟɪɢɦɟɧɬɚɥɶɧɨɦ ɚɥɝɨɪɢɬɦɟ ɱɟɬɤɨ ɨɱɟɪɱɟɧɧɵɯ ɫɬɚɞɢɣ (ɲɚɝɨɜ) ɩɨɡɜɨɥɹɟɬ ɩɪɢ ɧɟɨɛɯɨɞɢɦɨɫɬɢ ɩɪɟɪɜɚɬɶ ɜɵɩɨɥɧɟɧɢɟ ɩɪɨɬɨɤɨɥɚ ɧɚ ɩɟɪɢɨɞ, ɩɪɟɜɵɲɚɸɳɢɣ ɞɚɠɟ 24 ɱɚɫɚ, ɛɟɡ ɭɳɟɪɛɚ ɞɥɹ ɰɟɥɨɫɬɧɨɫɬɢ ɩɪɨɛɵ. Ɍɚɤɢɦɢ ɬɨɱɤɚɦɢ ɩɪɟɪɵɜɚɧɢɹ ɢ ɯɪɚɧɟɧɢɹ ɦɨɝɭɬ ɛɵɬɶ ɫɥɟɞɭɸɳɢɟ. 1. ɏɪɚɧɟɧɢɟ IPG-ɫɬɪɢɩɨɜ ɩɨɫɥɟ ɷɥɟɤɬɪɨɮɨɪɟɡɚ ɜ ɩɟɪɜɨɦ ɧɚɩɪɚɜ12 ɥɟɧɢɢ. IPG-ɫɬɪɢɩɵ ɞɨɥɠɧɵ ɛɵɬɶ ɡɚɳɢɳɟɧɵ ɨɬ ɮɢɡɢɱɟɫɤɨɝɨ ɩɨɜɪɟɠɞɟɧɢɹ (ɧɚɩɪɢɦɟɪ, ɰɟɥɥɨɮɚɧɨɦ) ɢ ɯɪɚɧɢɬɶɫɹ ɩɪɢ ɬɟɦɩɟɪɚɬɭɪɟ –20°C. Ɂɚɦɨɪɚɠɢɜɚɧɢɟ ɨɛɪɚɡɰɚ ɩɪɟɞɨɬɜɪɚɳɚɟɬ ɞɢɮɮɭɡɢɸ ɢɡɨɷɥɟɤɬɪɢɱɟɫɤɢ ɮɨɤɭɫɢɪɨɜɚɧɧɵɯ ɛɟɥɤɨɜ ɢɡ ɫɬɪɢɩɨɜ. Ɉɬɬɚɢɜɚɧɢɟ ɫɥɟɞɭɟɬ ɩɪɨɢɡɜɨɞɢɬɶ ɩɪɢ ɤɨɦɧɚɬɧɨɣ ɬɟɦɩɟɪɚɬɭɪɟ. Ɏɚɤɬɢɱɟɫɤɢ, ɷɬɚ ɬɨɱɤɚ ɩɪɟɪɵɜɚɧɢɹ ɹɜɥɹɟɬɫɹ ɩɟɪɜɨɣ, ɤɨɝɞɚ ɩɪɨɛɚ ɦɨɠɟɬ ɯɪɚɧɢɬɶɫɹ ɛɟɡ ɧɚɪɭɲɟɧɢɹ ɫɜɨɟɣ ɰɟɥɨɫɬɧɨɫɬɢ, ɬɟɦ ɛɨɥɟɟ, ɱɬɨ ɩɪɨɞɨɥɠɢɬɟɥɶɧɨɫɬɶ ɨɩɵɬɚ ɨɬ ɫɛɨɪɚ ɤɥɟɬɨɤ ɞɨ ɷɥɟɤɬɪɨɮɨɪɟɡɚ ɜ ɩɟɪɜɨɦ ɧɚɩɪɚɜɥɟɧɢɢ ɫɨɫɬɚɜɥɹɟɬ ɩɪɢɦɟɪɧɨ ɨɞɢɧ ɪɚɛɨɱɢɣ ɞɟɧɶ. 2. MALDI-ɩɥɚɬɵ, ɫɨɞɟɪɠɚɳɢɟ ɦɚɬɪɢɰɭ, ɫɦɟɲɚɧɧɭɸ ɫ ɩɟɪɟɜɚɪɟɧɧɵɦ ɛɟɥɤɨɦ, ɦɨɝɭɬ ɯɪɚɧɢɬɶɫɹ ɩɪɢ ɤɨɦɧɚɬɧɨɣ ɬɟɦɩɟɪɚɬɭɪɟ, ɛɭɞɭɱɢ ɝɟɪɦɟɬɢɱɧɨ ɭɤɭɩɨɪɟɧɧɵɦɢ. Ɍɚɤɨɣ ɨɛɪɚɡɟɰ ɦɨɠɟɬ ɯɪɚɧɢɬɶɫɹ ɞɨɫɬɚɬɨɱɧɨ ɞɨɥɝɨ ɩɟɪɟɞ MALDI-ɚɧɚɥɢɡɨɦ. ɗɬɨɬ ɦɨɦɟɧɬ ɜɪɟɦɟɧɢ (ɩɨɫɥɟ ɨɬɛɨɪɚ ɛɟɥɤɨɜɵɯ ɩɹɬɟɧ ɢ ɢɯ ɩɟɪɟɜɚɪɢɜɚɧɢɹ) ɢɞɟɚɥɟɧ ɞɥɹ ɨɫɬɚɧɨɜɤɢ ɩɟɪɟɞ MALDI-ɢɞɟɧɬɢɮɢɤɚɰɢɟɣ. Ɍɚɤɢɦ ɨɛɪɚɡɨɦ, ɜɟɫɶ ɷɤɫɩɟɪɢɦɟɧɬɚɥɶɧɵɣ ɚɥɝɨɪɢɬɦ ɭɞɨɛɧɨ ɪɚɡɞɟɥɢɬɶ ɧɚ ɞɜɟ ɪɚɛɨɱɢɟ ɮɚɡɵ ɛɟɡ ɭɳɟɪɛɚ ɞɥɹ ɰɟɥɨɫɬɧɨɫɬɢ ɢɡɭɱɚɟɦɨɝɨ ɨɛɪɚɡɰɚ. Ɇɟɬɨɞɵ ɩɪɨɬɟɨɦɧɨɝɨ ɚɧɚɥɢɡɚ ɧɚɰɟɥɟɧɵ ɧɚ ɩɪɨɪɚɛɨɬɤɭ ɞɜɭɯ ɜɚɪɢɚɧɬɨɜ ɫɨɜɟɪɲɟɧɫɬɜɨɜɚɧɢɹ ɫɤɪɢɧɢɧɝɚ, ɞɢɚɝɧɨɫɬɢɤɢ ɢ ɦɨɧɢɬɨɪɢɧɝɚ ɪɚɡɥɢɱɧɵɯ ɡɚɛɨɥɟɜɚɧɢɣ. ɉɟɪɜɵɣ ɩɪɟɞɫɬɚɜɥɹɟɬ ɫɨɛɨɣ ɢɞɟɚɥɶɧɭɸ ɫɯɟɦɭ ɪɟɲɟɧɢɹ ɩɪɨɛɥɟɦɵ ɱɟɪɟɡ ɨɬɤɪɵɬɢɟ ɬ.ɧ. «ɛɢɨɦɚɪɤɟɪɨɜ» – ɬɚɤɢɯ ɜɟɳɟɫɬɜ, ɤɨɬɨɪɵɟ ɩɨɹɜɥɹɸɬɫɹ ɜ ɬɤɚɧɹɯ ɢ ɛɢɨɥɨɝɢɱɟɫɤɢɯ ɠɢɞɤɨɫɬɹɯ ɨɪɝɚɧɢɡɦɚ ɬɨɥɶɤɨ ɩɪɢ ɫɬɪɨɝɨ ɨɩɪɟɞɟɥɟɧɧɵɯ ɩɚɬɨɥɨɝɢɱɟɫɤɢɯ ɩɪɨɰɟɫɫɚɯ, ɥɟɝɤɨ ɞɟɬɟɤɬɢɪɭɸɬɫɹ ɫɨɜɪɟɦɟɧɧɵɦɢ ɛɢɨɯɢɦɢɱɟɫɤɢɦɢ ɩɪɢɥɨɠɟɧɢɹɦɢ ɢ ɫ ɦɚɤɫɢɦɚɥɶɧɨ ɜɵɫɨɤɨɣ ɞɨɥɟɣ ɜɟɪɨɹɬɧɨɫɬɢ ɫɜɢɞɟɬɟɥɶɫɬɜɭɸɬ ɨ ɤɨɧɤɪɟɬɧɨɦ ɡɚɛɨɥɟɜɚɧɢɢ ɩɪɢ ɨɛɧɚɪɭɠɟɧɢɢ ɭ ɤɨɧɤɪɟɬɧɨɝɨ ɩɚɰɢɟɧɬɚ. Ⱦɟɬɟɤɰɢɹ ɬɚɤɨɝɨ ɛɢɨɦɚɪɤɟɪɚ ɜɨ ɜɡɹɬɵɯ ɞɥɹ ɚɧɚɥɢɡɚ ɛɢɨɥɨɝɢɱɟɫɤɢɯ ɨɛɪɚɡɰɚɯ ɦɨɠɟɬ ɥɟɱɶ ɜ ɨɫɧɨɜɭ ɞɢɚɝɧɨɫɬɢɱɟɫɤɨɝɨ ɬɟɫɬɚ, ɨɛɥɚɞɚɸɳɟɝɨ ɫɚ13 ɦɵɦ ɩɪɨɝɪɟɫɫɢɜɧɵɦ ɫɨɱɟɬɚɧɢɟɦ ɨɩɟɪɚɰɢɨɧɧɵɯ ɯɚɪɚɤɬɟɪɢɫɬɢɤ – ɱɭɜɫɬɜɢɬɟɥɶɧɨɫɬɢ, ɫɩɟɰɢɮɢɱɧɨɫɬɢ, ɬɨɱɧɨɫɬɢ, ɜɨɫɩɪɨɢɡɜɨɞɢɦɨɫɬɢ ɪɟɡɭɥɶɬɚɬɨɜ ɢ ɞɪ. [42]. Ɉɞɧɚɤɨ ɜ ɪɟɚɥɶɧɨɫɬɢ «ɨɬɪɚɛɨɬɚɬɶ» ɢɞɟɚɥɶɧɵɣ ɛɢɨɦɚɪɤɟɪ ɞɥɹ ɤɚɠɞɨɣ ɧɨɡɨɥɨɝɢɱɟɫɤɨɣ ɟɞɢɧɢɰɵ ɩɨɤɚ ɧɟ ɭɞɚɟɬɫɹ. ɑɚɳɟ ɝɨɜɨɪɹɬ ɨ «ɩɪɨɬɟɨɦɧɵɯ ɩɪɨɮɚɣɥɚɯ» – ɰɟɥɵɯ ɫɩɟɤɬɪɚɯ ɞɨɜɨɥɶɧɨ ɫɩɟɰɢɮɢɱɧɵɯ ɛɟɥɤɨɜ ɢ ɩɟɩɬɢɞɨɜ, ɤɨɬɨɪɵɟ ɯɚɪɚɤɬɟɪɧɵ ɞɥɹ ɬɟɯ ɢɥɢ ɢɧɵɯ ɩɚɬɨɥɨɝɢɱɟɫɤɢɯ ɫɨɫɬɨɹɧɢɣ ɫ ɦɢɧɢɦɚɥɶɧɨɣ ɢɧɞɢɜɢɞɭɚɥɶɧɨ-ɬɢɩɨɥɨɝɢɱɟɫɤɨɣ ɪɚɡɧɢɰɟɣ. ɋɩɟɰɢɮɢɱɧɨɫɬɶ ɩɪɨɮɚɣɥɚ ɞɥɹ ɤɨɧɤɪɟɬɧɨɝɨ ɡɚɛɨɥɟɜɚɧɢɹ (ɢɯ ɝɪɭɩɩɵ) ɨɰɟɧɢɜɚɸɬ ɧɚ ɨɫɧɨɜɚɧɢɢ ɩɚɬɨɥɨɝɢɱɟɫɤɢɯ ɢɡɦɟɧɟɧɢɣ ɫɨɞɟɪɠɚɧɢɹ ɜ ɨɛɪɚɡɰɟ ɩɪɨɬɟɢɧɨɜ ɜ ɨɩɪɟɞɟɥɟɧɧɵɯ ɞɢɚɩɚɡɨɧɚɯ ɦɚɫɫ, ɩɪɟɨɛɥɚɞɚɧɢɹ ɥɢɛɨ ɧɟɞɨɫɬɚɬɨɱɧɨɫɬɢ ɩɨɥɢɩɟɩɬɢɞɨɜ ɨɩɪɟɞɟɥɟɧɧɵɯ ɝɪɭɩɩ, ɦɧɨɠɟɫɬɜɟɧɧɨɫɬɢ ɚɧɨɦɚɥɶɧɵɯ ɢɡɨɮɨɪɦ/ ɬɪɚɧɫɮɨɪɦɚɰɢɣ ɫɯɨɞɧɨɝɨ ɨɛɪɚɡɚ ɞɥɹ ɪɚɡɧɵɯ ɛɟɥɤɨɜ. ɍɠɟ ɫɨɡɞɚɧɵ ɛɚɡɵ ɞɚɧɧɵɯ ɩɨ ɫɨɬɧɹɦ ɛɟɥɤɨɜ ɩɪɨɬɟɨɦɚ ɦɢɨɤɚɪɞɚ, ɭɪɨɜɧɢ ɤɨɬɨɪɵɯ ɢɡɦɟɧɹɸɬɫɹ ɩɪɢ ɯɪɨɧɢɱɟɫɤɢɯ ɢ ɨɫɬɪɵɯ ɫɟɪɞɟɱɧɨɫɨɫɭɞɢɫɬɵɯ ɩɚɬɨɥɨɝɢɹɯ [17]. Ɉɛɧɚɪɭɠɟɧɨ, ɱɬɨ ɩɪɢ ɬɚɤɢɯ ɩɚɬɨɥɨɝɢɹɯ ɜɨɡɪɚɫɬɚɸɬ ɤɨɧɰɟɧɬɪɚɰɢɢ ɬ.ɧ. ɛɟɥɤɨɜ ɬɟɩɥɨɜɨɝɨ ɲɨɤɚ (heat-shock proteins – HSP), ɛɟɥɤɨɜ ɦɢɬɨɯɨɧɞɪɢɣ, ɚ ɬɚɤɠɟ ɛɟɥɤɨɜ, ɜɨɜɥɟɱɟɧɧɵɯ ɜ ɝɟɧɟɪɢɪɨɜɚɧɢɟ ɷɧɟɪɝɢɢ. 1.2. ɋɬɜɨɥɨɜɵɟ ɤɥɟɬɤɢ, ɚɬɟɪɨɫɤɥɟɪɨɡ ɢ ɩɪɨɬɟɨɦɢɤɚ ɋɟɪɞɟɱɧɨ-ɫɨɫɭɞɢɫɬɚɹ ɫɢɫɬɟɦɚ ɫɨɫɬɨɢɬ (ɋɋɋ) ɢɡ ɛɨɥɶɲɨɝɨ ɤɨɥɢɱɟɫɬɜɚ ɫɩɟɰɢɚɥɢɡɢɪɭɸɳɢɯɫɹ ɤɥɟɬɨɱɧɵɯ ɬɢɩɨɜ, ɜɤɥɸɱɚɹ ɦɢɨɰɢɬɵ, ɮɢɛɪɨɛɥɚɫɬɵ, ɨɫɬɟɨɛɥɚɫɬɵ, ɧɟɣɪɨɧɵ, ɷɧɞɨɬɟɥɢɚɥɶɧɵɟ ɢ ɝɥɚɞɤɨɦɵɲɟɱɧɵɟ ɤɥɟɬɤɢ, ɚ ɬɚɤɠɟ ɫɬɜɨɥɨɜɵɟ ɢ ɩɪɨɝɟɧɢɬɨɪɧɵɟ ɤɥɟɬɤɢ. Ʉ ɫɨɠɚɥɟɧɢɸ, ɩɪɨɬɟɨɦ ɛɨɥɶɲɢɧɫɬɜɚ ɷɬɢɯ ɤɥɟɬɨɤ ɤ ɧɚɫɬɨɹɳɟɦɭ ɜɪɟɦɟɧɢ ɢɡɭɱɟɧ ɧɟɞɨɫɬɚɬɨɱɧɨ ɢ ɦɚɥɨɢɡɜɟɫɬɧɨɣ ɨɫɬɚɟɬɫɹ ɟɝɨ ɫɜɹɡɶ ɫ ɩɚɬɨɥɨɝɢɱɟɫɤɢɦɢ ɫɨɫɬɨɹɧɢɹɦɢ ɫɚɦɨɣ ɫɢɫɬɟɦɵ. 14 Ɍɟɦ ɧɟ ɦɟɧɟɟ, ɧɟɞɚɜɧɢɟ ɤɥɢɧɢɱɟɫɤɢɟ ɢɫɫɥɟɞɨɜɚɧɢɹ ɩɨɤɚɡɵɜɚɸɬ, ɱɬɨ ɧɟɞɢɮɮɟɪɟɧɰɢɪɨɜɚɧɧɵɟ ɤɥɟɬɤɢ, ɰɢɪɤɭɥɢɪɭɸɳɢɟ ɜ ɤɪɨɜɨɬɨɤɟ, ɢɦɟɸɬ ɨɝɪɨɦɧɵɣ ɩɨɬɟɧɰɢɚɥ ɞɥɹ ɪɟɝɟɧɟɪɚɰɢɢ ɫɨɫɭɞɢɫɬɨɣ ɬɤɚɧɢ [76]. Ɉɧɢ ɩɚɬɪɭɥɢɪɭɸɬ ɨɪɝɚɧɢɡɦ ɢ ɦɢɝɪɢɪɭɸɬ ɤ ɦɟɫɬɭ, ɝɞɟ ɨɛɧɚɪɭɠɢɜɚɸɬ ɩɨɜɪɟɠɞɟɧɢɟ ɫɨɫɭɞɚ. Ɉɞɧɚɤɨ, ɧɟɩɨɫɪɟɞɫɬɜɟɧɧɨ ɮɭɧɤɰɢɨɧɚɥɶɧɨɟ ɢɯ ɞɟɣɫɬɜɢɟ ɡɚɜɢɫɢɬ ɨɬ ɦɧɨɝɢɯ ɮɚɤɬɨɪɨɜ, ɬɚɤɢɯ, ɤɚɤ ɫɩɨɫɨɛɧɨɫɬɶ ɩɪɢɤɪɟɩɥɹɬɶɫɹ ɤ ɷɧɞɨɬɟɥɢɸ, ɦɢɝɪɢɪɨɜɚɬɶ, ɪɚɡɦɧɨɠɚɬɶɫɹ, ɩɨɞɞɟɪɠɢɜɚɬɶ ɫɨɛɫɬɜɟɧɧɭɸ ɠɢɡɧɟɫɩɨɫɨɛɧɨɫɬɶ. ɂɡɜɟɫɬɧɨ, ɱɬɨ ɩɪɢ ɞɢɚɛɟɬɟ ɭɯɭɞɲɚɟɬɫɹ ɮɭɧɤɰɢɨɧɢɪɨɜɚɧɢɟ ɬɚɤ ɧɚɡɵɜɚɟɦɵɯ ɤɥɟɬɨɤ-ɩɪɟɞɲɟɫɬɜɟɧɧɢɤɨɜ ɷɧɞɨɬɟɥɢɹ ɢ ɩɨɞɚɜɥɹɟɬɫɹ ɦɢɝɪɚɰɢɹ ɦɨɧɨɰɢɬɨɜ, ɢɦɟɸɳɚɹ ɜɚɠɧɨɟ ɡɧɚɱɟɧɢɹ ɞɥɹ ɜɨɫɫɬɚɧɨɜɥɟɧɢɹ ɫɨɫɭɞɨɜ ɢ ɨɛɪɚɡɨɜɚɧɢɹ ɩɚɪɚɥɥɟɥɶɧɵɯ ɩɟɪɢɮɟɪɢɱɟɫɤɢɯ ɫɨɫɭɞɨɜ ɜ ɫɥɭɱɚɟ ɩɨɜɪɟɠɞɟɧɢɹ [97]. Ⱥɬɟɪɨɫɤɥɟɪɨɡ ɹɜɥɹɟɬɫɹ ɨɞɧɨɣ ɢɡ ɧɚɢɛɨɥɟɟ ɜɚɠɧɵɯ ɦɟɞɢɤɨɫɨɰɢɚɥɶɧɵɯ ɩɪɨɛɥɟɦ, ɢ ɟɝɨ ɤɥɢɧɢɱɟɫɤɢɟ ɩɪɨɹɜɥɟɧɢɹ ɡɚɧɢɦɚɸɬ ɜɟɞɭɳɟɟ ɦɟɫɬɨ ɜ ɫɬɪɭɤɬɭɪɟ ɡɚɛɨɥɟɜɚɟɦɨɫɬɢ ɢ ɫɦɟɪɬɧɨɫɬɢ. Ɍɳɚɬɟɥɶɧɵɣ ɚɧɚɥɢɡ ɛɟɥɤɨɜ ɢɡ ɩɨɪɚɠɟɧɧɨɣ ɚɬɟɪɨɫɤɥɟɪɨɡɨɦ ɬɤɚɧɢ ɚɪɬɟɪɢɣ ɦɨɝ ɛɵ ɨɛɧɚɪɭɠɢɬɶ ɜɢɞɵ ɛɟɥɤɨɜ, ɤɨɬɨɪɵɟ ɭɱɚɫɬɜɭɸɬ ɜ ɫɨɫɭɞɢɫɬɨɦ ɪɟɦɨɞɟɥɢɪɨɜɚɧɢɢ ɢ ɚɬɟɪɨɝɟɧɟɡɟ. ɂɞɟɧɬɢɮɢɤɚɰɢɹ ɱɟɥɨɜɟɱɟɫɤɨɝɨ ɚɬɟɪɨɫɤɥɟɪɨɬɢɱɟɫɤɨɝɨ ɩɪɨɬɟɨɦɚ – ɮɭɧɞɚɦɟɧɬ ɞɥɹ ɞɚɥɶɧɟɣɲɢɯ ɢɫɫɥɟɞɨɜɚɧɢɣ, ɨɫɧɨɜɚ ɞɥɹ ɩɨɫɬɪɨɟɧɢɹ ɢ ɩɪɨɜɟɪɤɢ ɧɨɜɵɯ ɝɢɩɨɬɟɡ. Ɉɱɟɜɢɞɧɨ, ɱɬɨ ɜɵɹɜɥɟɧɢɟ ɮɭɧɤɰɢɨɧɚɥɶɧɨɣ ɫɜɹɡɢ ɦɟɠɞɭ ɚɬɟɪɨɫɤɥɟɪɨɬɢɱɟɫɤɢɦɢ ɩɨɪɚɠɟɧɢɹɦɢ ɢ ɩɪɨɬɟɨɦɧɵɦ ɩɪɨɮɢɥɟɦ ɢɧɬɢɦɵ ɚɨɪɬɵ ɱɟɥɨɜɟɤɚ ɢɦɟɟɬ ɢɫɤɥɸɱɢɬɟɥɶɧɨɟ ɡɧɚɱɟɧɢɟ ɞɥɹ ɩɨɧɢɦɚɧɢɹ ɢɧɢɰɢɢɪɭɸɳɢɯ ɩɪɢɱɢɧ ɜɨɡɧɢɤɧɨɜɟɧɢɹ ɚɬɟɪɨɫɤɥɟɪɨɡɚ. Ɉɞɧɚɤɨ ɞɨ ɧɚɫɬɨɹɳɟɝɨ ɜɪɟɦɟɧɢ ɥɢɲɶ ɜ ɨɱɟɧɶ ɧɟɛɨɥɶɲɨɦ ɤɨɥɢɱɟɫɬɜɟ ɪɚɛɨɬ ɛɵɥɢ ɢɫɫɥɟɞɨɜɚɧɵ ɛɟɥɤɢ, ɜɵɞɟɥɟɧɧɵɟ ɢɡ ɚɬɟɪɨɫɤɥɟɪɨɬɢɱɟɫɤɢɯ ɛɥɹɲɟɤ ɚɨɪɬɵ ɱɟɥɨɜɟɤɚ [29, 31, 56]. Ɉɫɨɛɵɣ ɢɧɬɟɪɟɫ ɩɪɢ ɩɪɨɜɟɞɟɧɢɢ ɞɚɥɶɧɟɣɲɢɯ ɢɫɫɥɟɞɨɜɚɧɢɣ ɩɪɟɞɫɬɚɜɥɹɸɬ ɩɪɨɬɟ15 ɨɦɧɵɟ ɩɪɨɮɢɥɢ ɢɧɬɢɦɵ ɢ ɦɟɞɢɢ ɚɪɬɟɪɢɣ ɩɪɢ ɪɚɡɧɵɯ ɫɬɚɞɢɹɯ ɚɬɟɪɨɫɤɥɟɪɨɬɢɱɟɫɤɨɝɨ ɩɨɪɚɠɟɧɢɹ. ɉɨɹɜɥɹɸɬɫɹ ɢ ɧɨɜɵɟ ɞɚɧɧɵɟ ɨɛ ɭɱɚɫɬɢɢ ɫɬɜɨɥɨɜɵɯ ɤɥɟɬɨɤ (ɋɄ) ɤɚɤ ɝɟɦɨɩɨɷɬɢɱɟɫɤɨɣ, ɬɚɤ ɢ ɫɬɪɨɦɚɥɶɧɨɣ ɥɢɧɢɣ ɞɢɮɮɟɪɟɧɰɢɪɨɜɤɢ, ɜ ɚɬɟɪɨɝɟɧɟɡɟ [7, 51, 58, 62]. Ɍɚɤɢɟ ɞɚɧɧɵɟ ɩɨɡɜɨɥɢɥɢ ɩɪɟɞɩɨɥɨɠɢɬɶ, ɱɬɨ ɜɚɠɧɵɦ ɦɨɦɟɧɬɨɦ ɜ ɪɚɡɜɢɬɢɢ ɚɬɟɪɨɫɤɥɟɪɨɡɚ ɹɜɥɹɟɬɫɹ ɩɪɨɧɢɤɧɨɜɟɧɢɟ ɤɨɥɨɧɢɟɨɛɪɚɡɭɸɳɢɯ ɫɬɜɨɥɨɜɵɯ ɤɥɟɬɨɤ ɝɟɦɨɩɨɷɬɢɱɟɫɤɨɣ ɢ ɫɬɪɨɦɚɥɶɧɨɣ ɥɢɧɢɣ ɞɢɮɮɟɪɟɧɰɢɪɨɜɤɢ ɜ ɢɧɬɢɦɭ ɜ ɦɟɫɬɚɯ ɤɨɧɰɟɧɬɪɚɰɢɢ ɥɢɩɢɞɨɜ. Ɉɛɧɚɪɭɠɟɧɢɟ ɝɟɦɨɩɨɷɬɢɱɟɫɤɢɯ ɢ ɫɬɪɨɦɚɥɶɧɵɯ ɫɬɜɨɥɨɜɵɯ ɤɥɟɬɨɤɩɪɟɞɲɟɫɬɜɟɧɧɢɤɨɜ ɜ ɢɧɬɢɦɟ ɚɬɟɪɨɦɚɬɨɡɧɨɣ ɚɨɪɬɵ ɱɟɥɨɜɟɤɚ ɫɜɢɞɟɬɟɥɶɫɬɜɭɟɬ ɨ ɰɢɪɤɭɥɹɰɢɢ ɷɬɢɯ ɤɥɟɬɨɤ ɜ ɤɪɨɜɨɬɨɤɟ [5, 6]. Ɇɟɬɨɞɚɦɢ ɤɥɨɧɚɥɶɧɨɝɨ ɤɭɥɶɬɢɜɢɪɨɜɚɧɢɹ ɢɧɬɢɦɚɥɶɧɵɯ ɤɥɟɬɨɤ ɢɡ ɚɬɟɪɨɫɤɥɟɪɨɬɢɱɟɫɤɢ ɢɡɦɟɧɟɧɧɵɯ ɭɱɚɫɬɤɨɜ ɚɪɬɟɪɢɣ ɛɵɥɢ ɨɛɧɚɪɭɠɟɧɵ ɫɬɜɨɥɨɜɵɟ ɤɨɥɨɧɢɟɨɛɪɚɡɭɸɳɢɟ ɤɥɟɬɤɢ, ɤɨɬɨɪɵɟ ɮɨɪɦɢɪɨɜɚɥɢ ɜ ɬɟɫɬɫɢɫɬɟɦɚɯ ɤɚɤ ɝɟɦɨɩɨɷɬɢɱɟɫɤɢɟ, ɬɚɤ ɢ ɫɬɪɨɦɚɥɶɧɵɟ ɤɨɥɨɧɢɢ. Ʉɥɟɬɤɢ ɜ ɫɮɨɪɦɢɪɨɜɚɧɧɵɯ ɫɬɪɨɦɚɥɶɧɵɯ ɤɨɥɨɧɢɹɯ ɫɢɧɬɟɡɢɪɨɜɚɥɢ ɤɨɥɥɚɝɟɧɨɜɵɣ ɮɢɛɪɢɥɥɹɪɧɵɣ ɢ ɨɫɬɟɨɢɞɧɵɣ ɦɚɬɪɢɤɫɵ [72]. Ʉɭɥɶɬɢɜɢɪɨɜɚɧɢɟ ɤɥɟɬɨɤ ɦɨɧɨɧɭɤɥɟɚɪɧɨɣ ɮɪɚɤɰɢɢ ɩɟɪɢɮɟɪɢɱɟɫɤɨɣ ɤɪɨɜɢ ɩɚɰɢɟɧɬɨɜ ɫ ɩɟɪɜɢɱɧɨɣ ɝɢɩɟɪɥɢɩɢɞɟɦɢɟɣ ɢ ɤɨɪɨɧɚɪɧɵɦ ɚɬɟɪɨɫɤɥɟɪɨɡɨɦ ɬɚɤɠɟ ɩɨɡɜɨɥɢɥɨ ɨɛɧɚɪɭɠɢɬɶ ɤɨɥɨɧɢɢ ɫɬɪɨɦɚɥɶɧɵɯ ɮɢɛɪɨɛɥɚɫɬɨɩɨɞɨɛɧɵɯ ɤɥɟɬɨɤ, ɤɨɬɨɪɵɟ ɫɢɧɬɟɡɢɪɨɜɚɥɢ ɮɢɛɪɢɥɥɹɪɧɵɣ ɢ ɨɫɬɟɨɢɞɧɵɣ ɜɧɟɤɥɟɬɨɱɧɵɣ ɦɚɬɪɢɤɫ [72]. ɗɬɢ ɞɚɧɧɵɟ ɞɚɸɬ ɨɫɧɨɜɚɧɢɟ ɩɨɥɚɝɚɬɶ, ɱɬɨ ɫɭɳɟɫɬɜɭɟɬ ɬɟɫɧɚɹ ɜɡɚɢɦɨɫɜɹɡɶ ɦɟɠɞɭ ɪɚɡɜɢɬɢɟɦ ɚɬɟɪɨɫɤɥɟɪɨɡɚ ɢ ɩɨɜɟɞɟɧɢɟɦ ɫɬɜɨɥɨɜɵɯ ɤɥɟɬɨɤ-ɩɪɟɞɲɟɫɬɜɟɧɧɢɤɨɜ. ɂɡ-ɡɚ ɨɝɪɚɧɢɱɟɧɧɨɣ ɫɩɨɫɨɛɧɨɫɬɢ ɫɟɪɞɟɱɧɨɣ ɦɵɲɰɵ ɤ ɜɨɫɫɬɚɧɨɜɥɟɧɢɸ, ɢɧɮɚɪɤɬ ɦɢɨɤɚɪɞɚ ɩɪɢɜɨɞɢɬ ɤ ɧɟɨɛɪɚɬɢɦɨɦɭ ɧɚɪɭɲɟɧɢɸ ɪɚɛɨɬɵ ɫɟɪɞɰɚ ɢ ɯɪɨɧɢɱɟɫɤɨɣ ɫɟɪɞɟɱɧɨɣ ɧɟɞɨɫɬɚɬɨɱɧɨɫɬɢ, ɧɟ ɩɨɞɞɚɸɳɟɣɫɹ ɯɢɪɭɪɝɢɱɟɫɤɨɦɭ ɢ ɮɚɪɦɚɤɨɥɨɝɢɱɟɫɤɨɦɭ ɥɟɱɟɧɢɸ. Ⱥɥɶɬɟɪɧɚɬɢ16 ɜɨɣ ɬɪɚɞɢɰɢɨɧɧɨɣ ɬɟɪɚɩɢɢ ɫɟɝɨɞɧɹ ɫɱɢɬɚɟɬɫɹ ɬɪɚɧɫɩɥɚɧɬɚɰɢɹ ɋɄ ɤɚɤ ɷɦɛɪɢɨɧɚɥɶɧɨɝɨ, ɬɚɤ ɢ ɩɨɫɬɧɚɬɚɥɶɧɨɝɨ ɩɪɨɢɫɯɨɠɞɟɧɢɹ. ȼ ɤɚɱɟɫɬɜɟ ɧɚɢɛɨɥɟɟ ɩɟɪɫɩɟɤɬɢɜɧɵɯ ɢɫɬɨɱɧɢɤɨɜ ɋɄ ɪɚɫɫɦɚɬɪɢɜɚɸɬɫɹ ɤɨɫɬɧɵɣ ɦɨɡɝ, ɦɨɛɢɥɢɡɨɜɚɧɧɚɹ ɩɟɪɢɮɟɪɢɱɟɫɤɚɹ ɤɪɨɜɶ, ɚ ɬɚɤɠɟ ɩɭɩɨɜɢɧɧɚɹ ɤɪɨɜɶ ɧɨɜɨɪɨɠɞɟɧɧɵɯ [35]. Ⱥɜɬɨɪɵ ɭɤɚɡɚɧɧɨɣ ɪɚɛɨɬɵ ɫɱɢɬɚɸɬ, ɱɬɨ ɧɟɨɛɯɨɞɢɦɨ ɜɵɹɫɧɢɬɶ, ɤɚɤɨɣ ɢɦɟɧɧɨ ɬɢɩ ɤɥɟɬɨɤ ɭɱɚɫɬɜɭɟɬ ɜ ɪɟɝɟɧɟɪɚɰɢɢ, ɚ ɬɚɤɠɟ ɪɚɡɪɚɛɨɬɚɬɶ ɦɟɬɨɞɵ ɫɬɢɦɭɥɹɰɢɢ ɞɚɧɧɵɯ ɤɥɟɬɨɤ ɜ ɭɫɥɨɜɢɹɯ in vitro ɞɨ ɜɜɟɞɟɧɢɹ ɜ ɨɪɝɚɧɢɡɦ, ɫ ɰɟɥɶɸ ɭɫɢɥɟɧɢɹ ɢɯ ɪɟɦɨɞɟɥɢɪɭɸɳɟɝɨ ɷɮɮɟɤɬɚ. ɗɬɢ ɷɤɫɩɟɪɢɦɟɧɬɵ ɹɜɥɹɸɬɫɹ ɨɞɧɢɦɢ ɢɡ ɩɟɪɜɵɯ ɫɜɢɞɟɬɟɥɶɫɬɜ ɩɟɪɫɩɟɤɬɢɜɧɨɫɬɢ ɧɨɜɵɯ ɩɨɞɯɨɞɨɜ ɩɨ ɫɬɢɦɭɥɹɰɢɢ ɪɟɝɟɧɟɪɚɬɢɜɧɨɢɧɞɭɤɰɢɨɧɧɵɯ ɫɜɨɣɫɬɜ ɝɟɦɨɩɨɷɬɢɱɟɫɤɢɯ ɫɬɜɨɥɨɜɵɯ ɤɥɟɬɨɤ. Ʉɚɤ ɧɚɦ ɩɪɟɞɫɬɚɜɥɹɟɬɫɹ, ɨɱɟɧɶ ɜɚɠɧɨ, ɱɬɨɛɵ ɛɵɥɨ ɩɪɨɞɨɥɠɟɧɨ ɢɡɭɱɟɧɢɟ ɩɪɨɬɟɨɦɚ ɋɄ, ɜɤɥɸɱɚɹ ɜɥɢɹɧɢɟ ɧɚ ɧɟɝɨ ɮɚɤɬɨɪɨɜ ɦɢɤɪɨɨɤɪɭɠɟɧɢɹ, ɨɩɪɟɞɟɥɹɸɳɢɯ ɞɚɥɶɧɟɣɲɟɟ ɪɚɡɜɢɬɢɟ ɢ ɮɭɧɤɰɢɨɧɢɪɨɜɚɧɢɟ ɋɄ. ɇɨ ɧɟ ɦɟɧɟɟ ɜɚɠɧɨ ɢ ɩɚɪɚɥɥɟɥɶɧɨɟ ɢɫɫɥɟɞɨɜɚɧɢɟ ɩɪɨɬɟɨɦɚ ɞɪɭɝɢɯ ɷɥɟɦɟɧɬɨɜ ɋɋɋ, ɩɚɬɨɥɨɝɢɱɟɫɤɢɟ ɢɡɦɟɧɟɧɢɹ ɜ ɤɨɬɨɪɨɣ ɧɟ ɦɨɝɭɬ ɧɟ ɡɚɬɪɨɧɭɬɶ ɦɧɨɝɢɟ ɟɟ ɤɨɦɩɨɧɟɧɬɵ, ɜɤɥɸɱɚɹ ɝɥɚɞɤɨɦɵɲɟɱɧɵɟ ɢ ɷɧɞɨɬɟɥɢɚɥɶɧɵɟ ɤɥɟɬɤɢ. ɉɪɟɞɫɬɚɜɥɹɟɬɫɹ, ɱɬɨ ɜɵɹɜɥɟɧɢɟ ɦɨɞɢɮɢɰɢɪɭɟɦɵɯ ɩɚɬɨɥɨɝɢɟɣ ɛɟɥɤɨɜ ɦɨɠɟɬ ɞɚɬɶ ɤɥɸɱ, ɤɚɤ ɤ ɩɨɧɢɦɚɧɢɸ ɦɟɯɚɧɢɡɦɨɜ ɡɚɛɨɥɟɜɚɧɢɣ, ɬɚɤ ɢ ɤ ɢɯ ɥɟɱɟɧɢɸ. ȼ ɞɚɧɧɵɣ ɦɨɦɟɧɬ ɬɚɤɢɯ ɷɤɫɩɟɪɢɦɟɧɬɨɜ, ɯɚɪɚɤɬɟɪɢɡɭɟɦɵɯ ɤɚɤ «ɮɭɧɤɰɢɨɧɚɥɶɧɚɹ ɩɪɨɬɟɨɦɢɤɚ», ɜɵɩɨɥɧɟɧɨ ɹɜɧɨ ɧɟɞɨɫɬɚɬɨɱɧɨ. Ɍɟɦ ɧɟ ɦɟɧɟɟ, ɫɨɨɬɜɟɬɫɬɜɭɸɳɟɟ ɩɨɜɟɞɟɧɢɟ ɛɟɥɤɨɜ, ɜɤɥɸɱɚɹ ɢɡɦɟɧɟɧɢɟ ɢɯ ɤɨɥɢɱɟɫɬɜɚ, ɢɡɭɱɚɥɨɫɶ ɩɪɢ ɤɚɪɞɢɨɦɢɨɩɚɬɢɹɯ ɱɟɥɨɜɟɤɚ ɢ ɠɢɜɨɬɧɵɯ ɢ ɜ ɪɹɞɟ ɞɪɭɝɢɯ ɫɥɭɱɚɟɜ. ɋɨɝɥɚɫɧɨ ɩɪɟɞɜɚɪɢɬɟɥɶɧɵɦ ɞɚɧɧɵɦ, ɧɚɢɛɨɥɟɟ ɨɛɟɳɚɸɳɢɦɢ ɦɚɪɤɟɪɚɦɢ ɞɥɹ ɤɚɪɞɢɨɩɪɨɬɟɨɦɢɤɢ ɦɨɝɭɬ ɛɵɬɶ ɬɪɨɩɨɧɢɧɵ, ɢɡɨɮɨɪɦɵ ɚɥɶɮɚ-1-ɮɢɛɪɢɧɨɝɟɧɚ, ɢɡɨɮɨɪɦɵ ɚɩɨɥɢɩɨɩɪɨɬɟɢɧɚ Ⱥ-1, ɋ-ɪɟɚɤɬɢɜɧɵɣ ɛɟɥɨɤ ɢ ɞɪ. [8,105]. 17 ɋ ɩɨɦɨɳɶɸ ɩɪɨɬɟɨɦɢɤɢ ɭɠɟ ɩɨɤɚɡɚɧɨ, ɱɬɨ ɨɤɢɫɥɟɧɧɵɟ Ʌɉɇɉ ɩɨɞɚɜɥɹɸɬ ɩɪɨɥɢɮɟɪɚɰɢɸ ɤɥɟɬɨɤ ɜ ɷɧɞɨɬɟɥɢɢ, ɱɬɨ ɨɛɴɹɫɧɹɟɬɫɹ, ɜɢɞɢɦɨ, ɦɨɞɢɮɢɤɚɰɢɟɣ ɛɟɥɤɨɜ (ɮɨɫɮɨɪɢɥɢɪɨɜɚɧɢɟɦ, ɚɜɬɨɞɟɝɪɚɞɚɰɢɟɣ ɢ/ɢɥɢ ɢɡɦɟɧɟɧɧɨɣ ɷɤɫɩɪɟɫɫɢɟɣ ɧɭɤɥɟɨɮɨɫɦɢɧɚ, ɫɬɚɬɦɢɧɚ ɢ ɧɭɤɥɟɨɥɢɧɚ ɩɪɢ ɭɫɥɨɜɢɹɯ ɨɤɢɫɥɢɬɟɥɶɧɨɝɨ ɫɬɪɟɫɫɚ) [3]. ɋɥɟɞɭɟɬ ɨɬɦɟɬɢɬɶ ɬɚɤɠɟ ɪɚɛɨɬɭ Gundry et. al. [36], ɩɨɫɜɹɳɟɧɧɭɸ ɛɟɥɤɚɦ ɩɨɜɟɪɯɧɨɫɬɢ ɋɄ ɢ ɢɯ ɩɨɬɟɧɰɢɚɥɶɧɨɣ ɪɨɥɢ ɜ ɪɟɝɟɧɟɪɚɬɢɜɧɨɣ ɦɟɞɢɰɢɧɟ ɋɋɋ. Ɇɨɠɧɨ ɩɪɟɞɩɨɥɨɠɢɬɶ, ɱɬɨ ɜ ɪɚɡɜɢɬɢɢ ɚɬɟɪɨɫɤɥɟɪɨɡɚ, ɚ ɢɦɟɧɧɨ ɜ ɩɨɩɵɬɤɟ ɥɨɤɚɥɢɡɚɰɢɢ ɢ ɥɢɤɜɢɞɚɰɢɢ ɜɨɫɩɚɥɢɬɟɥɶɧɨɝɨ ɩɪɨɰɟɫɫɚ ɜ ɫɬɟɧɤɟ ɫɨɫɭɞɚ, ɢɫɩɨɥɶɡɭɟɬɫɹ ɭɧɢɜɟɪɫɚɥɶɧɵɣ ɦɟɯɚɧɢɡɦ ɬɤɚɧɟɜɨɣ ɪɟɝɟɧɟɪɚɰɢɢ ɫ ɭɱɚɫɬɢɟɦ ɜ ɧɟɦ ɩɨɥɢɩɨɬɟɧɬɧɵɯ ɋɄ. ɉɪɨɧɢɤɧɨɜɟɧɢɟ ɷɬɢɯ ɭɧɢɜɟɪɫɚɥɶɧɵɯ ɤɥɟɬɨɤ ɜ ɢɧɬɢɦɭ ɢ ɩɨɫɥɟɞɭɸɳɚɹ ɪɟɚɥɢɡɚɰɢɹ ɩɪɢɫɭɳɟɣ ɢɦ ɩɨɥɢɩɨɬɟɧɬɧɨɫɬɢ ɦɨɝɭɬ ɛɵɬɶ ɩɪɢɱɢɧɨɣ ɮɨɪɦɢɪɨɜɚɧɢɹ ɛɥɹɲɟɤ ɪɚɡɧɨɝɨ ɝɟɧɟɡɚ. Ʌɨɤɚɥɶɧɨɟ ɦɢɤɪɨɨɤɪɭɠɟɧɢɟ ɦɨɠɟɬ ɨɩɪɟɞɟɥɹɬɶ ɞɢɮɮɟɪɟɧɰɢɪɨɜɤɭ ɫɬɜɨɥɨɜɵɯ ɤɨɥɨɧɢɟɨɛɪɚɡɭɸɳɢɯ ɤɥɟɬɨɤ ɜ ɪɚɡɥɢɱɧɨɦ ɧɚɩɪɚɜɥɟɧɢɢ ɢ ɛɵɬɶ ɩɪɢɱɢɧɨɣ ɧɟ ɬɨɥɶɤɨ ɮɢɛɪɨɡɚ ɜ ɢɧɬɢɦɟ ɫɨɫɭɞɢɫɬɨɣ ɫɬɟɧɤɢ, ɧɨ ɢ ɯɨɧɞɪɨ- ɢɥɢ ɨɫɬɟɨɝɟɧɟɡɚ ɫ ɩɨɫɥɟɞɭɸɳɟɣ ɤɚɥɶɰɢɮɢɤɚɰɢɟɣ. Ɉɬɦɟɬɢɦ ɜ ɷɬɨɣ ɫɜɹɡɢ, ɱɬɨ ɜ ɩɟɪɢɮɟɪɢɱɟɫɤɨɣ ɤɪɨɜɢ ɩɚɰɢɟɧɬɨɜ ɫ ɞɨɤɭɦɟɧɬɢɪɨɜɚɧɧɵɦ ɚɬɟɪɨɫɤɥɟɪɨɡɨɦ (ɜ ɨɬɥɢɱɢɟ ɨɬ ɡɞɨɪɨɜɵɯ ɞɨɛɪɨɜɨɥɶɰɟɜ) ɩɨɤɚɡɚɧɨ ɜɵɫɨɤɨɟ ɫɨɞɟɪɠɚɧɢɟ ɰɢɪɤɭɥɢɪɭɸɳɢɯ ɩɪɟɨɫɬɟɨɤɥɚɫɬɨɜ. ɗɬɨɬ ɮɟɧɨɦɟɧ, ɩɨ-ɜɢɞɢɦɨɦɭ, ɫɜɹɡɚɧ ɫ ɩɪɨɰɟɫɫɨɦ ɤɚɥɶɰɢɮɢɤɚɰɢɢ ɜ ɫɬɟɧɤɟ ɫɨɫɭɞɚ, ɧɟɩɨɫɪɟɞɫɬɜɟɧɧɵɦɢ ɭɱɚɫɬɧɢɤɚɦɢ ɤɨɬɨɪɨɝɨ ɹɜɥɹɸɬɫɹ ɨɫɬɟɨɛɥɚɫɬɵ. ɉɪɟɞɩɨɥɚɝɚɟɬɫɹ, ɱɬɨ ɨɫɬɟɨɛɥɚɫɬɵ ɦɨɝɭɬ ɩɪɨɢɫɯɨɞɢɬɶ ɥɢɛɨ ɢɡ ɋɄ, ɩɪɨɧɢɤɚɸɳɢɯ ɜ ɚɬɟɪɨɫɤɥɟɪɨɬɢɱɟɫɤɢɟ ɛɥɹɲɤɢ ɢɡ ɤɪɨɜɹɧɨɝɨ ɪɭɫɥɚ ɢɥɢ ɢɡ ɩɥɸɪɢɩɨɬɟɧɬɧɵɯ ɆɋɄ, ɤɨɬɨɪɵɟ ɨɫɬɚɸɬɫɹ ɜ ɚɪɬɟɪɢɚɥɶɧɨɣ ɫɬɟɧɤɟ ɧɚ ɷɦɛɪɢɨɧɚɥɶɧɨɣ ɫɬɚɞɢɢ ɪɚɡɜɢɬɢɹ. Ɉɫɬɟɨɛɥɚɫɬɵ, ɹɜɥɹɹɫɶ ɜɚɠɧɵɦɢ ɤɨɦɩɨɧɟɧɬɚɦɢ «ɧɢɲɢ» ȽɋɄ, ɥɟɝɤɨ ɪɟɚɝɢɪɭɸɬ ɧɚ ɜɧɟɲɧɢɟ 18 ɫɬɢɦɭɥɵ, ɱɬɨ ɩɪɢɜɨɞɢɬ ɤ ɜɨɡɞɟɣɫɬɜɢɸ ɧɚ ȽɋɄ ɩɨɫɪɟɞɫɬɜɨɦ ɪɟɰɟɩɬɨɪɨɜ, ɰɢɬɨɤɢɧɨɜ ɢ ɮɚɤɬɨɪɨɜ ɪɨɫɬɚ. Ʉɨɦɛɢɧɢɪɭɹ ɞɨɫɬɢɠɟɧɢɹ ɛɢɨɥɨɝɢɢ ɋɄ ɢ ɡɧɚɧɢɹ ɢɯ ɩɪɨɬɟɨɦɚ, ɦɨɠɧɨ ɩɨɧɹɬɶ ɦɟɯɚɧɢɡɦɵ ɢɯ ɩɪɨɥɢɮɟɪɚɰɢɢ ɢ ɫɚɦɨɨɛɧɨɜɥɟɧɢɹ, ɚ ɬɚɤɠɟ ɧɚɩɪɚɜɢɬɶ ɞɢɮɮɟɪɟɧɰɢɚɰɢɸ ɜ ɠɟɥɚɟɦɨɟ ɪɭɫɥɨ. ɗɬɨ ɩɨɡɜɨɥɢɬ ɭɬɨɱɧɢɬɶ ɫɩɨɫɨɛɵ ɦɚɧɢɩɭɥɹɰɢɢ ɫ ɋɄ ɢ ɪɟɚɥɢɡɨɜɚɬɶ ɦɨɳɧɵɣ ɬɟɪɚɩɟɜɬɢɱɟɫɤɢɣ ɩɨɬɟɧɰɢɚɥ ɷɬɢɯ ɭɧɢɤɚɥɶɧɵɯ ɤɥɟɬɨɤ. 1.3. Ƚɟɦɨɩɨɷɬɢɱɟɫɤɢɟ ɫɬɜɨɥɨɜɵɟ ɤɥɟɬɤɢ ɤɚɤ ɨɛɴɟɤɬ ɢɫɫɥɟɞɨɜɚɧɢɹ ɢ ɢɫɩɨɥɶɡɨɜɚɧɢɹ ɜ ɩɚɬɨɮɢɡɢɨɥɨɝɢɢ Ƚɟɦɨɩɨɷɬɢɱɟɫɤɢɟ ɫɬɜɨɥɨɜɵɟ ɤɥɟɬɤɢ (ȽɋɄ) ɩɪɢɧɚɞɥɟɠɚɬ ɤ ɋɄ, ɩɨɞɜɟɪɝɚɟɦɵɦ ɜ ɩɨɫɥɟɞɧɢɟ ɝɨɞɵ ɜɫɟ ɛɨɥɟɟ ɦɚɫɲɬɚɛɧɨɦɭ ɢɡɭɱɟɧɢɸ. Ɂɚ ɫɩɨɫɨɛɧɨɫɬɶ ɝɟɧɟɪɢɪɨɜɚɬɶ ɛɨɥɟɟ ɩɨɥɭɞɸɠɢɧɵ ɬɢɩɨɜ ɤɥɟɬɨɤ ɤɪɨɜɢ (ɪɢɫ. 1.1) ȽɋɄ ɩɪɢɧɹɬɨ ɧɚɡɵɜɚɬɶ ɦɭɥɶɬɢɩɨɬɟɧɬɧɵɦɢ ɋɄ [88,68,103]. Ɇɟɯɚɧɢɡɦɵ, ɩɨɫɪɟɞɫɬɜɨɦ ɤɨɬɨɪɵɯ ɨɫɭɳɟɫɬɜɥɹɟɬɫɹ ɜɡɚɢɦɨɞɟɣɫɬɜɢɟ ȽɋɄ ɫɨ ɫɜɨɢɦ ɦɢɤɪɨɨɤɪɭɠɟɧɢɟɦ, ɢɥɢ ɫ ɬ.ɧ. ɧɢɲɟɣ, ɞɨ ɫɢɯ ɩɨɪ ɩɨɧɹɬɧɵ ɞɚɥɟɤɨ ɧɟ ɩɨɥɧɨɫɬɶɸ. ȼ ɷɬɨɣ ɫɜɹɡɢ ɜɨɡɦɨɠɧɨɫɬɶ ɤɭɥɶɬɢɜɢɪɨɜɚɧɢɹ ȽɋɄ ɞɥɹ ɢɯ ɩɨɫɥɟɞɭɸɳɟɝɨ ɢɡɭɱɟɧɢɹ ɢ ɢɫɩɨɥɶɡɨɜɚɧɢɹ ɥɢɦɢɬɢɪɭɟɬɫɹ ɫɩɨɫɨɛɧɨɫɬɶɸ ɦɚɧɢɩɭɥɢɪɨɜɚɬɶ ɫ ɷɬɢɦɢ ɤɥɟɬɤɚɦɢ in vitro. Ⱦɨ ɫɢɯ ɩɨɪ ɫɭɳɟɫɬɜɭɟɬ ɜɟɫɶɦɚ ɨɝɪɚɧɢɱɟɧɧɨɟ ɱɢɫɥɨ ɫɩɨɫɨɛɨɜ ɤɭɥɶɬɢɜɢɪɨɜɚɧɢɹ, ɤɨɬɨɪɵɟ ɩɨɡɜɨɥɹɸɬ ɩɨɞɞɟɪɠɢɜɚɬɶ ɢ ɪɚɡɦɧɨɠɚɬɶ ȽɋɄ in vitro, ɩɪɢ ɷɬɨɦ ɫɨɯɪɚɧɹɟɬɫɹ ɧɟɩɨɥɧɨɟ ɡɧɚɧɢɟ ɨ ɜɥɢɹɧɢɢ ɪɚɡɥɢɱɧɵɯ ɭɫɥɨɜɢɣ ɤɭɥɶɬɢɜɢɪɨɜɚɧɢɹ ɧɚ ɛɟɥɤɨɜɵɣ ɫɨɫɬɚɜ ɤɥɟɬɨɤ. ɂɧɮɨɪɦɚɰɢɹ ɨ ɫɨɫɬɚɜɟ ȽɋɄ ɜ ɢɯ ɟɫɬɟɫɬɜɟɧɧɨɦ ɫɨɫɬɨɹɧɢɢ ɦɨɝɥɚ ɛɵ ɫɩɨɫɨɛɫɬɜɨɜɚɬɶ ɨɩɬɢɦɢɡɚɰɢɢ ɷɬɢɯ ɭɫɥɨɜɢɣ ɢ ɩɨɥɭɱɟɧɢɸ ɢɫɬɢɧɧɨ ɝɨɦɨɝɟɧɧɨɣ ɩɨɩɭɥɹɰɢɢ ȽɋɄ. ɇɟɭɞɢɜɢɬɟɥɶɧɨ, ɱɬɨ ɦɧɨɝɢɟ ɪɚɛɨɬɵ ɩɨ 19 ȽɋɄ ɛɵɥɢ ɩɨɫɜɹɳɟɧɵ ɢɯ ɩɨɜɟɞɟɧɢɸ ɤɚɤ ɩɨɩɭɥɹɰɢɢ ɜ ɧɚɬɭɪɚɥɶɧɨɣ ɧɢɲɟ ɤɨɫɬɧɨɝɨ ɦɨɡɝɚ, ɩɪɟɞɨɩɪɟɞɟɥɹɸɳɟɣ ɢɯ ɛɟɥɤɨɜɵɣ ɫɨɫɬɚɜ. Ɋɢɫ. 1.1. ɋɯɟɦɚ ɝɟɦɨɩɨɷɡɚ ɇɚɩɪɢɦɟɪ, ɦɨɠɧɨ ɨɠɢɞɚɬɶ, ɱɬɨ Jagged1 (Jag1), ɜɵɞɟɥɹɟɦɵɣ ɨɫɬɟɨɛɥɚɫɬɚɦɢ ɜ ɨɬɜɟɬ ɧɚ ɨɛɪɚɛɨɬɤɭ ɉɌȽ (ɮɪɚɝɦɟɧɬɵ 1-34), ɜɥɢɹɟɬ ɧɚ ȽɋɄ ɩɨ ɫɢɝɧɚɥɶɧɨɦɭ ɩɭɬɢ ɱɟɪɟɡ ɪɟɰɟɩɬɨɪ Notch-1 [24, 107]. Ɍɚɤɢɦ ɨɛɪɚɡɨɦ, Jagged1 ɹɜɥɹɟɬɫɹ ɨɞɧɢɦ ɢɡ ɧɚɢɛɨɥɟɟ ɜɚɠɧɵɯ ɮɚɤɬɨɪɨɜ, ɨɩɪɟɞɟɥɹɸɳɢɯ ɩɭɬɶ ɪɚɡɜɢɬɢɹ ȽɋɄ. ɂɞɟɧɬɢɮɢɤɚɰɢɹ ɛɟɥɤɨɜ (ɬɚɤɢɯ, ɤɚɤ Jag1 ɢ ɞɪɭɝɢɯ, ɫɜɹɡɚɧɧɵɯ ɫ Notch-1), ɧɚɪɹɞɭ ɫ ɭɬɨɱɧɟɧɢɟɦ ɪɨɥɢ ɞɪɭɝɢɯ ɜɧɟɲɧɢɯ ɮɚɤɬɨɪɨɜ, ɩɨɡɜɨɥɹɟɬ ɨɩɪɟɞɟɥɢɬɶ ɜɫɟ ɜɨɡɦɨɠɧɨɫɬɢ ɤɨɧɬɪɨɥɹ ȽɋɄ. 20 ȼɧɟɲɧɢɟ ɮɚɤɬɨɪɵ, ɭɱɚɫɬɜɭɸɳɢɟ ɜ ɪɟɝɭɥɹɰɢɢ ȽɋɄ, ɹɜɥɹɸɬɫɹ ɱɚɫɬɶɸ ɧɢɲɢ ɋɄ. ɂɫɫɥɟɞɨɜɚɧɢɹ ɩɨ ɯɨɭɦɢɧɝɭ ȽɋɄ, ɦɟɱɟɧɵɯ ɡɟɥɟɧɵɦ ɮɥɭɨɪɟɫɰɢɪɭɸɳɢɦ ɛɟɥɤɨɦ (GFP), ɩɨɫɥɟ ɬɪɚɧɫɩɥɚɧɬɚɰɢɢ ɭɤɚɡɵɜɚɸɬ ɧɚ ɩɨɜɟɪɯɧɨɫɬɶ ɷɧɞɨɫɬɢɥɹ ɤɚɤ ɜɨɡɦɨɠɧɭɸ ɧɢɲɭ ɋɄ [66]. ɇɨ ɫɚɦɵɣ ɫɟɪɶɟɡɧɵɣ ɜɵɜɨɞ ɢɡ ɷɬɢɯ ɷɤɫɩɟɪɢɦɟɧɬɨɜ ɩɨ ɯɨɭɦɢɧɝɭ – ɜɚɠɧɨɫɬɶ ɨɫɬɟɨɛɥɚɫɬɨɜ ɜ ɮɭɧɤɰɢɨɧɢɪɨɜɚɧɢɢ ɧɢɲɢ ȽɋɄ ɜ ɤɨɫɬɧɨɦ ɦɨɡɝɟ [24, 107]. 1.3.1. Ɋɟɝɭɥɹɬɨɪɵ ȽɋɄ ȼ ɧɚɫɬɨɹɳɟɟ ɜɪɟɦɹ ɜɚɠɧɨɫɬɶ Notch ɜ ɫɢɝɧɚɥɢɡɚɰɢɢ ɩɪɢ ɝɟɦɚɬɨɩɨɷɡɟ ɩɪɟɞɫɬɚɜɥɹɟɬɫɹ ɧɟɫɨɦɧɟɧɧɨɣ. ɗɤɫɩɪɟɫɫɢɹ ɚɤɬɢɜɢɪɨɜɚɧɧɨɝɨ Notch1, ɨɩɨɫɪɟɞɨɜɚɧɧɚɹ ɪɟɬɪɨɜɢɪɭɫɨɦ, ɭɜɟɥɢɱɢɜɚɥɚ ɫɤɨɪɨɫɬɶ ɫɚɦɨɨɛɧɨɜɥɟɧɢɹ ɤɥɟɬɨɤ-ɩɪɟɞɲɟɫɬɜɟɧɧɢɤɨɜ ɝɟɦɨɩɨɷɡɚ ɜ ɩɪɢɫɭɬɫɬɜɢɢ ɫɨɨɬɜɟɬɫɬɜɭɸɳɢɯ ɰɢɬɨɤɢɧɨɜ, ɱɬɨ ɭɤɚɡɵɜɚɟɬ ɧɚ ɩɨɬɟɧɰɢɚɥɶɧɭɸ ɫɩɨɫɨɛɧɨɫɬɶ Notch ɭɫɢɥɢɜɚɬɶ ɫɚɦɨɨɛɧɨɜɥɟɧɢɟ ɋɄ [93]. ȼ ɞɪɭɝɢɯ ɪɚɛɨɬɚɯ ɩɨɤɚɡɚɧɨ, ɱɬɨ ɤɨɥɢɱɟɫɬɜɨ ɤɥɟɬɨɤ- ɩɪɟɞɲɟɫɬɜɟɧɧɢɤɨɜ ɝɟɦɨɩɨɷɡɚ ɜɨɡɪɚɫɬɚɥɨ ɩɨɫɥɟ ɤɭɥɶɬɢɜɢɪɨɜɚɧɢɹ ɫ ɥɢɝɚɧɞɨɦ ɪɟɰɟɩɬɨɪɚ Notch, ɩɪɢɫɭɬɫɬɜɭɸɳɢɦ ɧɚ ɩɨɜɟɪɯɧɨɫɬɢ ɤɥɟɬɨɤ, ɢɥɢ ɫ ɥɢɝɚɧɞɚɦɢ Notch, ɬɚɤɢɦɢ, ɤɚɤ Delta-1, Jagged-1, ɢɥɢ Jagged-2, ɜ ɪɚɫɬɜɨɪɟ [37, 43, 46,45, 47, 89,94, 100]. ɉɪɢ ɢɧɤɭɛɚɰɢɢ ɦɵɲɢɧɵɯ ɝɟɦɚɬɨɩɨɷɬɢɱɟɫɤɢɯ ɤɥɟɬɨɤ- ɩɪɟɞɲɟɫɬɜɟɧɧɢɤɨɜ, ɫɬɢɦɭɥɢɪɨɜɚɧɧɵɯ ɰɢɬɨɤɢɧɚɦɢ, ɫ Delta-1, ɢɦɦɨɛɢɥɢɡɨɜɚɧɧɵɦ ɧɚ ɩɨɜɟɪɯɧɨɫɬɢ ɩɥɚɫɬɢɤɨɜɵɯ ɱɚɲɟɤ, ɧɚɛɥɸɞɚɥɚɫɶ ɢɯ ɛɵɫɬɪɚɹ ɷɤɫɩɚɧɫɢɹ, ɚ ɬɪɚɧɫɩɥɚɧɬɚɰɢɹ ɬɚɤɢɯ ɤɭɥɶɬɢɜɢɪɨɜɚɧɧɵɯ ɤɥɟɬɨɤ ɩɪɢɜɨɞɢɥɚ ɤ ɥɨɝɚɪɢɮɦɢɱɟɫɤɨɦɭ ɪɨɫɬɭ ɱɢɫɥɚ ɤɨɪɨɬɤɨɠɢɜɭɳɢɯ ɤɥɟɬɨɤ, ɜɨɫɫɬɚɧɚɜɥɢɜɚɸɳɢɯ ɤɨɫɬɧɵɣ ɦɨɡɝ [95]. Ɉɞɧɚɤɨ ɢɦɟɧɧɨ Jagged-1, ɚ ɧɟ Delta-1, ɩɪɟɞɫɬɚɜɥɹɟɬɫɹ ɝɥɚɜɧɵɦ ɥɢɝɚɧɞɨɦ ɪɟɰɟɩɬɨɪɚ Notch, ɷɤɫɩɪɟɫɫɢɪɭɟɦɵɦ ɫɬɪɨɦɚɥɶɧɵɦɢ ɤɥɟɬɤɚɦɢ ɤɨɫɬɧɨɝɨ ɦɨɡɝɚ [70,94]. 21 Vas ɫ ɫɨɬɪɭɞɧɢɤɚɦɢ [96] ɩɨɤɚɡɚɥ, ɱɬɨ ɢɦɦɨɛɢɥɢɡɚɰɢɹ Jagged-1 ɥɢɛɨ ɧɚ ɫɬɪɨɦɚɥɶɧɨɦ ɫɥɨɟ, ɥɢɛɨ ɧɚ ɦɢɤɪɨɫɮɟɪɚɯ Sepharose-4B ɧɟɨɛɯɨɞɢɦɚ ɞɥɹ ɢɧɞɭɤɰɢɢ ɫɚɦɨɨɛɧɨɜɥɟɧɢɹ ȽɋɄ. Ɂɚɦɟɬɢɦ, ɱɬɨ ɫɜɨɛɨɞɧɵɣ, ɪɚɫɬɜɨɪɢɦɵɣ Jagged-1 ɨɛɥɚɞɚɟɬ ɞɨɦɢɧɚɧɬɧɨ-ɨɬɪɢɰɚɬɟɥɶɧɵɦ ɞɟɣɫɬɜɢɟɦ ɧɚ ɫɚɦɨɨɛɧɨɜɥɟɧɢɟ ɜ ɤɨɦɩɚɪɬɦɟɧɬɟ ɪɚɧɧɢɯ ɩɪɨɝɟɧɢɬɨɪɧɵɯ ɤɥɟɬɨɤ, ɩɪɟɞɩɨɥɨɠɢɬɟɥɶɧɨ ɡɚ ɫɱɟɬ ɫɟɤɜɟɫɬɢɪɨɜɚɧɢɹ ɪɟɰɟɩɬɨɪɚ Notch ɢ ɩɪɟɞɨɬɜɪɚɳɟɧɢɹ ɜɡɚɢɦɨɞɟɣɫɬɜɢɹ Notch ɫ ɢɦɦɨɛɢɥɢɡɨɜɚɧɧɵɦ ɥɢɝɚɧɞɨɦ [96]. ɏɨɬɹ ɦɧɨɝɨɱɢɫɥɟɧɧɵɟ ɞɚɧɧɵɟ ɫɜɢɞɟɬɟɥɶɫɬɜɭɸɬ ɨ ɜɨɜɥɟɱɟɧɢɢ Notch-ɫɢɝɧɚɥɢɡɚɰɢɢ ɜ ɩɨɞɞɟɪɠɚɧɢɟ ɢ/ɢɥɢ ɫɚɦɨɨɛɧɨɜɥɟɧɢɟ ȽɋɄ, ɧɟɬ ɨɞɧɨɡɧɚɱɧɵɯ ɞɨɤɚɡɚɬɟɥɶɫɬɜ ɥɢɝɚɧɞ-ɢɧɞɭɰɢɪɨɜɚɧɧɨɣ ɫɚɦɨɨɛɧɨɜɥɹɸɳɟɣɫɹ ɩɪɨɥɢɮɟɪɚɰɢɢ ȽɋɄ, ɜɟɞɭɳɟɣ ɤ ɢɯ ɞɨɥɝɨɫɪɨɱɧɨɣ ɫɩɨɫɨɛɧɨɫɬɢ ɤ ɪɟɩɨɩɭɥɹɰɢɢ [96]. Kertesz ɫ ɫɨɬɪɭɞɧɢɤɚɦɢ [48] ɩɨɤɚɡɚɥ, ɱɬɨ ɢɧɞɭɰɢɪɨɜɚɧɧɚɹ ɢɦɦɨɛɢɥɢɡɨɜɚɧɧɵɦ Jagged-1 ɚɤɬɢɜɚɰɢɹ Notch ɜ ɤɭɥɶɬɭɪɟ ɤɥɟɬɨɤ ɤɨɫɬɧɨɝɨ ɦɨɡɝɚ ɥɢɧɟɣɧɵɯ ɦɵɲɟɣ ɫɭɳɟɫɬɜɟɧɧɨ ɭɜɟɥɢɱɢɜɚɟɬ ɫɩɨɫɨɛɧɨɫɬɶ ɤ ɪɟɩɨɩɭɥɹɰɢɢ ȽɋɄ ɜ ɩɪɢɫɭɬɫɬɜɢɢ ɫɨɨɬɜɟɬɫɬɜɭɸɳɢɯ ɰɢɬɨɤɢɧɨɜ, ɚ ɢɦɟɧɧɨ ɮɚɤɬɨɪɚ ɫɬɜɨɥɨɜɵɯ ɤɥɟɬɨɤ (SCF), ɥɢɝɚɧɞɚ Flk-2/Flt-3 (FL) ɢ ɬɪɨɦɛɨɩɪɨɬɟɢɧɚ (TPO) [48]. ɇɚɤɨɩɥɟɧɢɟ ȽɋɄ ɦɨɠɟɬ ɛɵɬɶ ɬɚɤɠɟ ɞɨɫɬɢɝɧɭɬɨ ɜ ɤɭɥɶɬɭɪɟ in vitro (14 ɞɧɟɣ) ɦɵɲɢɧɵɯ ɤɥɟɬɨɤ ɤɨɫɬɧɨɝɨ ɦɨɡɝɚ ɜ ɫɪɟɞɟ ɫ ɞɨɛɚɜɥɟɧɢɟɦ ɬɪɟɯ ɪɚɧɟɟ ɭɩɨɦɹɧɭɬɵɯ ɰɢɬɨɤɢɧɨɜ (SCF, ɥɢɝɚɧɞɚ Flk-2/Flt-3, TPO) ɢ ɢɦɦɨɛɢɥɢɡɨɜɚɧɧɨɝɨ ɥɢɝɚɧɞɚ Notch (Jagged-1) ɜ ɮɨɪɦɟ ɦɢɤɪɨɫɮɟɪ Sepharose-4B, ɩɨɤɪɵɬɵɯ Jagged-1 («Jag1 ɦɢɤɪɨɫɮɟɪ») [96]. Ⱥɛɫɨɥɸɬɧɨɟ ɱɢɫɥɨ ɝɟɦɨɩɨɷɬɢɱɟɫɤɢɯ ɤɥɟɬɨɤ ɫɨ ɫɩɨɫɨɛɧɨɫɬɶɸ ɤ ɞɨɥɝɨɫɪɨɱɧɨɣ ɪɟɩɨɩɭɥɹɰɢɢ ɭɜɟɥɢɱɢɜɚɥɨɫɶ ɜ 10–20 ɪɚɡ ɜ ɩɪɢɫɭɬɫɬɜɢɢ ɦɭɥɶɬɢɜɚɥɟɧɬɧɨɝɨ ɥɢɝɚɧɞɚ Notch. ɗɬɢ ɪɟɡɭɥɶɬɚɬɵ ɭɤɚɡɵɜɚɸɬ ɧɚ ɤɨɦɛɢɧɢɪɨɜɚɧɧɨɟ ɜɥɢɹɧɢɟ Notch ɢ ɰɢɬɨɤɢɧɨɜ ɧɚ ɩɭɬɢ ɫɢɝɧɚɥɢɡɚ22 ɰɢɢ, ɪɟɝɭɥɢɪɭɸɳɢɟ ɪɚɡɜɢɬɢɟ ȽɋɄ, ɚ ɬɚɤɠɟ ɧɚ ɩɨɬɟɧɰɢɚɥɶɧɭɸ ɪɨɥɶ ɥɢɝɚɧɞɚ Notch ɜ ɜɨɡɪɚɫɬɚɧɢɢ ȽɋɄ ɩɪɢ ɬɪɚɧɫɩɥɚɧɬɚɰɢɢ ɋɄ ɜ ɤɥɢɧɢɤɟ [48]. ɗɮɮɟɤɬɵ ɨɫɬɟɨɛɥɚɫɬɨɜ ɧɚ ȽɋɄ ɹɜɥɹɸɬɫɹ ɬɨɣ ɫɬɚɪɬɨɜɨɣ ɬɨɱɤɨɣ, ɢɫɯɨɞɹ ɢɡ ɤɨɬɨɪɨɣ ɩɪɨɬɟɨɦɢɤɚ ɞɚɟɬ ɜɨɡɦɨɠɧɨɫɬɶ ɢɫɫɥɟɞɨɜɚɬɶ ɪɨɥɶ ɨɫɬɟɨɛɥɚɫɬɨɜ ɜ ɩɪɨɥɢɮɟɪɚɰɢɢ ȽɋɄ. ɉɨɢɫɤ ɮɚɤɬɨɪɨɜ, ɤɨɬɨɪɵɟ ɫɩɨɫɨɛɫɬɜɭɸɬ ɪɚɡɦɧɨɠɟɧɢɸ ȽɋɄ ɜ ɤɭɥɶɬɭɪɟ, ɩɪɨɜɨɞɢɥɫɹ ɫ ɢɫɩɨɥɶɡɨɜɚɧɢɟɦ ɢɦɦɨɛɢɥɢɡɨɜɚɧɧɨɝɨ Jag1 [96]. ɉɪɢ ɷɬɨɦ Jag1-ɫɮɟɪɵ ɢɦɢɬɢɪɨɜɚɥɢ ɞɟɣɫɬɜɢɟ ɨɫɬɟɨɛɥɚɫɬɨɜ ɜ ɧɢɲɟ ȽɋɄ. ɇɚɛɥɸɞɚɟɦɵɟ ɷɮɮɟɤɬɵ ɭɫɢɥɢɥɢ ɩɨɡɢɰɢɢ ɬɟɯ, ɤɬɨ ɫɱɢɬɚɟɬ, ɱɬɨ ɩɨɧɢɦɚɧɢɟ ɪɨɥɢ ɦɢɤɪɨɨɤɪɭɠɟɧɢɹ ȽɋɄ ɫɨɜɟɪɲɟɧɧɨ ɧɟɨɛɯɨɞɢɦɨ ɞɥɹ ɩɨɥɭɱɟɧɢɹ ɜɨɡɦɨɠɧɨɫɬɢ ɭɩɪɚɜɥɟɧɢɹ ɪɚɡɦɧɨɠɟɧɢɟɦ ȽɋɄ in vitro. Ɉɩɪɟɞɟɥɢɜ ɧɢɲɭ ɤɚɤ ɞɟɬɟɪɦɢɧɚɧɬɭ ɜ ɪɟɝɭɥɹɰɢɢ ȽɋɄ, ɪɨɥɶ ɜɧɭɬɪɟɧɧɢɯ ɫɢɝɧɚɥɨɜ ɩɪɟɞɫɬɚɜɥɹɟɬɫɹ ɫ ɧɨɜɨɣ ɬɨɱɤɢ ɡɪɟɧɢɹ, ɧɟ ɬɨɥɶɤɨ ɤɚɤ ɪɟɝɭɥɢɪɭɸɳɢɯ ɫɚɦɢ ɩɨ ɫɟɛɟ, ɧɨ ɢ ɜɨ ɜɡɚɢɦɨɞɟɣɫɬɜɢɢ ɫ ɞɪɭɝɢɦɢ ɢɧɫɬɪɭɦɟɧɬɚɦɢ ɞɥɹ ɫɨɜɦɟɫɬɧɨɝɨ ɜɥɢɹɧɢɹ ɤɨɦɩɨɧɟɧɬɨɜ ɧɢɲɢ ɧɚ ɮɭɧɤɰɢɨɧɢɪɨɜɚɧɢɟ ɋɄ. 1.3.2. Ⱥɥɶɬɟɪɧɚɬɢɜɧɵɟ ɢɫɬɨɱɧɢɤɢ ȽɋɄ ɂɫɩɨɥɶɡɨɜɚɧɢɟ ȽɋɄ ɧɟ ɢɡ ɤɨɫɬɧɨɝɨ ɦɨɡɝɚ, ɚ ɢɡ ɞɪɭɝɢɯ ɢɫɬɨɱɧɢɤɨɜ ɩɪɢɜɟɥɨ ɤ ɫɞɜɢɝɭ ɬɟɪɦɢɧɨɥɨɝɢɢ ɨɬ ɬɪɚɧɫɩɥɚɧɬɚɰɢɢ ɤɨɫɬɧɨɝɨ ɦɨɡɝɚ ɤ ɬɪɚɧɫɩɥɚɧɬɚɰɢɢ ȽɋɄ (Ɍ-ȽɋɄ) [87]. Ɉɛɧɚɪɭɠɟɧɢɟ ȽɋɄ ɜ ɩɭɩɨɜɢɧɧɨɣ ɤɪɨɜɢ ɞɚɥɨ ɬɨɥɱɨɤ ɤ ɢɫɩɨɥɶɡɨɜɚɧɢɸ ɷɬɢɯ ɤɥɟɬɨɤ ɜ Ɍ-ȽɋɄ, ɨɛ ɭɫɩɟɲɧɨɫɬɢ ɤɨɬɨɪɨɣ ɫɨɨɛɳɢɥɢ Gluckman ɫ ɫɨɬɪɭɞɧɢɤɚɦɢ ɜ 1989 ɝ. [87, 32]. Ȼɚɧɤɢ ɡɚɦɨɪɨɠɟɧɧɵɯ ɤɥɟɬɨɤ ɢɡ ɩɭɩɨɜɢɧɧɨɣ ɤɪɨɜɢ (ɉɄ) ɫɟɣɱɚɫ – ɨɛɵɱɧɨɟ ɹɜɥɟɧɢɟ [32,33, 75,87]. ɋɨɨɛɳɚɟɬɫɹ, ɱɬɨ ȽɋɄ ɢɡ ɉɄ ɦɨɝɭɬ ɛɵɬɶ ɢɦɦɭɧɨɥɨɝɢɱɟɫɤɢ ɧɟɡɪɟɥɵ ɢ ɧɟ ɜɵɡɵɜɚɬɶ ɡɚɛɨɥɟɜɚɧɢɹ «ɬɪɚɧɫɩɥɚɧɬɚɬ ɩɪɨɬɢɜ ɯɨɡɹɢɧɚ» (GVHD), ɢɦɟɬɶ ɜɵɫɨɤɭɸ ɩɪɨɥɢɮɟɪɚɬɢɜɧɭɸ ɢ ɤɨɥɨɧɢɟɨɛɪɚɡɭɸɳɭɸ ɫɩɨɫɨɛɧɨɫɬɶ ɢ ɪɟɚɝɢɪɨɜɚɬɶ ɧɚ ɮɚɤɬɨɪɵ ɪɨɫɬɚ 23 [87]. ȼ ɨɬɥɢɱɢɟ ɨɬ ɤɥɟɬɨɤ ɢɡ ɤɨɫɬɧɨɝɨ ɦɨɡɝɚ, ɬɪɚɧɫɩɥɚɧɬɚɰɢɹ ȽɋɄ ɩɪɟɞɫɬɚɜɥɹɟɬɫɹ ɦɟɧɟɟ ɩɨɞɜɟɪɠɟɧɧɨɣ ɨɫɥɨɠɧɟɧɢɹɦ [34, 87]. ȽɋɄ ɢɡ ɉɄ ɨɛɵɱɧɨ ɩɨɥɭɱɚɸɬ ɩɪɢ ɪɨɠɞɟɧɢɢ ɪɟɛɟɧɤɚ. Ɂɚɬɟɦ ȽɋɄ ɯɪɚɧɹɬ ɜ ɛɚɧɤɟ ɫɬɜɨɥɨɜɵɯ ɤɥɟɬɨɤ ɞɥɹ ɩɨɫɥɟɞɭɸɳɟɝɨ ɢɫɩɨɥɶɡɨɜɚɧɢɹ ɜ ɬɟɪɚɩɟɜɬɢɱɟɫɤɢɯ ɰɟɥɹɯ. ɗɬɢ ɤɥɟɬɤɢ ɦɨɝɭɬ ɩɪɢɦɟɧɹɬɶɫɹ ɞɥɹ ɜɨɡɞɟɣɫɬɜɢɹ ɤɚɤ ɧɚ ɫɚɦɢɯ ɞɨɧɨɪɨɜ, ɬɚɤ ɢ ɧɚ ɞɪɭɝɢɯ ɩɚɰɢɟɧɬɨɜ, ɚ ɬɚɤɠɟ ɜ ɢɫɫɥɟɞɨɜɚɬɟɥɶɫɤɢɯ ɰɟɥɹɯ. Ɉɫɧɨɜɧɵɦ ɦɚɪɤɟɪɨɦ ȽɋɄ ɹɜɥɹɟɬɫɹ CD34 – ɛɟɥɨɤ, ɩɪɢɫɭɬɫɬɜɭɸɳɢɣ ɧɚ ɢɯ ɩɨɜɟɪɯɧɨɫɬɢ ɜɦɟɫɬɟ ɫ ɧɟɤɨɬɨɪɵɦɢ ɞɪɭɝɢɦɢ ɦɨɥɟɤɭɥɚɦɢ (ɧɚɩɪɢɦɟɪ, ɪɟɰɟɩɬɨɪɨɦ ɞɥɹ ɬ.ɧ. ɮɚɤɬɨɪɚ ɫɬɜɨɥɨɜɵɯ ɤɥɟɬɨɤ). ɉɨɞɨɛɧɵɣ ɮɟɧɨɬɢɩ ɯɚɪɚɤɬɟɪɢɡɭɟɬ ȽɋɄ ɜɧɟ ɡɚɜɢɫɢɦɨɫɬɢ ɨɬ ɢɯ ɢɫɬɨɱɧɢɤɚ: ɤɨɫɬɧɨɝɨ ɦɨɡɝɚ, ɩɟɪɢɮɟɪɢɱɟɫɤɨɣ ɢɥɢ ɩɭɩɨɜɢɧɧɨɣ ɤɪɨɜɢ. Ⱥ ɜɨɬ ɩɨ ɫɩɨɫɨɛɧɨɫɬɢ ɤ ɩɪɨɥɢɮɟɪɚɰɢɢ ɢ ɮɨɪɦɢɪɨɜɚɧɢɸ ɤɨɥɨɧɢɣ ɩɪɢ ɤɭɥɶɬɢɜɢɪɨɜɚɧɢɢ in vitro ɫɬɜɨɥɨɜɵɟ ɤɥɟɬɤɢ ɩɭɩɨɜɢɧɧɨɣ ɤɪɨɜɢ ɡɧɚɱɢɬɟɥɶɧɨ ɩɪɟɜɨɫɯɨɞɹɬ ɤɥɟɬɤɢ ɢɡ ɞɪɭɝɢɯ ɢɫɬɨɱɧɢɤɨɜ. Ʌɢɦɢɬɢɪɭɸɳɢɣ ɮɚɤɬɨɪ ɞɥɹ ɩɨɥɭɱɟɧɢɹ ɞɨɫɬɚɬɨɱɧɨɝɨ ɤɨɥɢɱɟɫɬɜɚ ȽɋɄ – ɢɯ ɤɨɥɢɱɟɫɬɜɨ ɜ ɨɛɪɚɡɰɚɯ, ɫɨɛɪɚɧɧɵɯ ɩɪɢ ɪɨɠɞɟɧɢɢ ɪɟɛɟɧɤɚ. ɉɪɢɡɧɚɧɧɵɦ ɦɟɞɢɰɢɧɫɤɢɦ ɮɚɤɬɨɦ ɹɜɥɹɟɬɫɹ ɢɯ ɩɪɢɝɨɞɧɨɫɬɶ ɬɨɥɶɤɨ ɞɥɹ ɬɟɪɚɩɢɢ ɩɚɰɢɟɧɬɨɜ ɫ ɜɟɫɨɦ 50 ɤɝ ɢɥɢ ɦɟɧɟɟ, ɬ.ɟ. ɞɥɹ ɞɟɬɟɣ ɜ ɜɨɡɪɚɫɬɟ ɩɪɢɦɟɪɧɨ 14 ɥɟɬ [20]. ȼ ɷɬɨɣ ɫɜɹɡɢ ɰɟɥɶɸ ɫɩɟɰɢɚɥɢɫɬɨɜ ɩɨ ɫɬɜɨɥɨɜɵɦ ɤɥɟɬɤɚɦ ɹɜɥɹɟɬɫɹ ɜɵɹɜɥɟɧɢɟ ɮɚɤɬɨɪɨɜ, ɪɟɝɭɥɢɪɭɸɳɢɯ ɮɭɧɤɰɢɨɧɢɪɨɜɚɧɢɟ ɋɄ ɜ ɢɯ ɟɫɬɟɫɬɜɟɧɧɨɦ ɨɤɪɭɠɟɧɢɢ. ɗɬɨ – ɩɭɬɶ ɤ ɦɚɧɢɩɭɥɢɪɨɜɚɧɢɸ ɫ ɋɄ, ɢ ɩɪɨɬɟɨɦɢɤɚ ɫɩɨɫɨɛɧɚ ɩɪɨɬɨɪɢɬɶ ɟɝɨ. Ɋɚɡɦɧɨɠɟɧɢɟ ȽɋɄ ɧɟ ɬɨɥɶɤɨ ɞɚɫɬ ɜɨɡɦɨɠɧɨɫɬɶ ɩɪɢɦɟɧɢɬɶ ɬɪɚɧɫɩɥɚɧɬɚɰɢɸ ȽɋɄ ɞɥɹ ɜɡɪɨɫɥɵɯ, ɧɨ ɢ ɩɨɡɜɨɥɢɬ ɞɨɫɬɢɱɶ ɞɪɭɝɢɯ ɤɥɢɧɢɱɟɫɤɢɯ ɩɪɟɢɦɭɳɟɫɬɜ ɞɥɹ ɪɟɰɢɩɢɟɧɬɨɜ. Ʉɥɟɬɨɱɧɚɹ ɞɨɡɚ ɬɪɚɧɫɩɥɚɧɬɚɬɚ ɉɄ ɫɨɯɪɚɧɹɟɬ ɤɥɸɱɟɜɨɟ ɡɧɚɱɟɧɢɟ ɞɥɹ ɫɤɨɪɨɫɬɢ ɩɪɢɠɢɜɥɟɧɢɹ ɢ ɜɵɠɢɜɚɧɢɹ. Ɇɢɧɢɦɚɥɶɧɨɣ ɞɨɡɨɣ ɹɞɟɪɧɵɯ ɤɥɟɬɨɤ ɹɜɥɹɟɬɫɹ ɜɟɥɢɱɢɧɚ 24 2,0×107 ɧɚ ɨɞɢɧ ɤɝ ɜɟɫɚ ɬɟɥɚ ɪɟɰɢɩɢɟɧɬɚ ɞɥɹ ɭɫɩɟɲɧɨɣ ɬɪɚɧɫɩɥɚɧɬɚɰɢɢ, ɫ ɭɱɟɬɨɦ ɬɨɝɨ, ɱɬɨ ɜ ɫɪɟɞɧɟɦ ɨɞɧɨ ɜɡɹɬɢɟ ɩɨɪɰɢɢ ɤɪɨɜɢ ɢɡ ɩɭɩɨɜɢɧɵ ɞɚɟɬ 1×109 ɧɚ ɨɞɢɧ ɤɝ. Ɍɚɤɢɦ ɨɛɪɚɡɨɦ, ɨɞɧɨɤɪɚɬɧɨɟ, ɜɡɹɬɢɟ ɚɭɬɨɥɨɝɢɱɧɨɣ ɤɪɨɜɢ ɧɟɞɨɫɬɚɬɨɱɧɨ ɞɥɹ ɥɸɛɵɯ ɩɚɰɢɟɧɬɨɜ, ɜɟɫ ɤɨɬɨɪɵɯ ɩɪɟɜɵɲɚɟɬ 50 ɤɝ. ɇɟɨɛɯɨɞɢɦɨ ɩɪɨɜɟɞɟɧɢɟ ɞɚɥɶɧɟɣɲɢɯ ɢɫɫɥɟɞɨɜɚɧɢɣ ɩɨ ɪɚɡɦɧɨɠɟɧɢɸ ȽɋɄ ex vivo, ɜɤɥɸɱɚɹ ɬɪɚɧɫɩɥɚɧɬɚɰɢɸ ɦɧɨɝɨɤɪɚɬɧɵɯ ɜɡɹɬɢɣ ɤɪɨɜɢ ɢɡ ɩɭɩɨɜɢɧɵ [20]. ɂɫɩɨɥɶɡɨɜɚɧɢɟ ɞɜɭɯ ɜɡɹɬɢɣ ɤɪɨɜɢ ɩɪɟɞɫɬɚɜɥɹɟɬɫɹ ɩɪɢɟɦɥɟɦɵɦ ɪɟɲɟɧɢɟɦ, ɨɞɧɚɤɨ ɱɚɫɬɨ ɛɵɜɚɟɬ ɬɪɭɞɧɨ ɧɚɣɬɢ ɷɬɢ ɞɜɚ ɨɛɪɚɡɰɚ ɤɪɨɜɢ ɞɥɹ ɩɚɰɢɟɧɬɚ ɢ ɨɫɭɳɟɫɬɜɢɬɶ ɭɫɩɟɲɧɨɟ ɩɪɢɠɢɜɥɟɧɢɟ. ɇɟɨɛɯɨɞɢɦɨɫɬɶ ɜ ɪɚɡɦɧɨɠɟɧɢɢ ȽɋɄ ɜ ɭɫɥɨɜɢɹɯ ɤɭɥɶɬɭɪɵ ɨɱɟɜɢɞɧɚ, ɨɫɨɛɟɧɧɨ ɟɫɥɢ ɫɭɳɟɫɬɜɭɟɬ ɩɨɬɪɟɛɧɨɫɬɶ ɢɫɩɨɥɶɡɨɜɚɬɶ ɋɄ ɧɨɜɨɪɨɠɞɟɧɧɨɝɨ ɞɥɹ ɩɨɫɥɟɞɭɸɳɟɝɨ ɢɯ ɩɪɢɦɟɧɟɧɢɹ ɜ ɛɨɥɟɟ ɡɪɟɥɨɦ ɜɨɡɪɚɫɬɟ. ɉɪɢɦɟɧɟɧɢɟ ɬɚɤɢɯ ɤɥɟɬɨɤ – ɨɛɧɚɞɟɠɢɜɚɸɳɚɹ ɩɟɪɫɩɟɤɬɢɜɚ, ɨɞɧɚɤɨ ɧɟɨɛɯɨɞɢɦɨ ɩɨɦɧɢɬɶ, ɱɬɨ, ɧɚɪɹɞɭ ɫ ɦɨɧɢɬɨɪɢɪɨɜɚɧɢɟɦ ɤɭɥɶɬɭɪɵ ɤɥɟɬɨɤ, ɫɥɟɞɭɟɬ ɢɦɟɬɶ ɪɟɮɟɪɟɧɫɧɵɟ ɬɨɱɤɢ ɞɥɹ ɤɨɧɬɪɨɥɹ ɜɫɟɯ ɩɚɪɚɦɟɬɪɨɜ ɫɢɫɬɟɦɵ, ɢ ɨɞɧɨɣ ɢɡ ɬɚɤɢɯ ɬɨɱɟɤ ɹɜɥɹɟɬɫɹ ɩɪɨɬɟɨɦ. ɇɟɜɨɡɦɨɠɧɨ ɢɡɛɟɠɚɬɶ ɢɡɦɟɧɟɧɢɹ ɛɟɥɤɚ ɩɪɢ ɤɭɥɶɬɢɜɢɪɨɜɚɧɢɢ ɤɥɟɬɨɤ. Ɉɞɢɧ ɢɡ ɫɩɨɫɨɛɨɜ ɤɨɧɬɪɨɥɹ ɡɚ ɯɨɞɨɦ ɷɬɢɯ ɢɡɦɟɧɟɧɢɣ – ɢɫɩɨɥɶɡɨɜɚɧɢɟ ɩɪɨɬɟɨɦɢɤɢ. Ɋɟɮɟɪɟɧɫɧɨɣ ɬɨɱɤɨɣ ɜ ɷɬɨɦ ɫɥɭɱɚɟ ɛɭɞɟɬ ɹɜɥɹɬɶɫɹ ɩɪɨɬɟɨɦ ȽɋɄ, ɜɵɞɟɥɟɧɧɵɣ ɢɡ ɨɛɪɚɡɰɚ ɩɭɩɨɜɢɧɧɨɣ ɤɪɨɜɢ. 1.3.3. Ʉɥɢɧɢɱɟɫɤɚɹ ɷɮɮɟɤɬɢɜɧɨɫɬɶ ɩɭɩɨɜɢɧɧɨɣ ɤɪɨɜɢ Ⱦɨɫɬɭɩɧɨɫɬɶ ɉɄ ɤɚɤ ɚɥɶɬɟɪɧɚɬɢɜɵ ɤɨɫɬɧɨɦɭ ɦɨɡɝɭ ɜ ɤɚɱɟɫɬɜɟ ɢɫɬɨɱɧɢɤɚ ȽɋɄ ɞɥɹ ɚɥɥɨɝɟɧɧɨɣ ɬɪɚɧɫɩɥɚɧɬɚɰɢɢ ɢɦɟɟɬ ɪɹɞ ɩɨɬɟɧɰɢɚɥɶɧɵɯ ɩɪɟɢɦɭɳɟɫɬɜ ɤɚɤ ɞɥɹ ɞɟɬɟɣ, ɬɚɤ ɢ ɞɥɹ ɜɡɪɨɫɥɵɯ ɜ ɤɥɢɧɢɱɟ- 25 ɫɤɨɣ ɩɪɚɤɬɢɤɟ ɩɨ ɫɪɚɜɧɟɧɢɸ ɫ ɞɪɭɝɢɦɢ ɢɫɬɨɱɧɢɤɚɦɢ ɚɥɥɨɝɟɧɧɵɯ ȽɋɄ [13,87]. ɗɬɢ ɩɪɟɢɦɭɳɟɫɬɜɚ ɜɤɥɸɱɚɸɬ ɜ ɫɟɛɹ ɛɨɥɟɟ ɛɵɫɬɪɭɸ ɞɨɫɬɭɩɧɨɫɬɶ ɦɚɬɟɪɢɚɥɚ, ɤɨɝɞɚ ɩɚɰɢɟɧɬɵ ɩɨɞɜɟɪɝɚɸɬɫɹ ɬɪɚɧɫɩɥɚɧɬɚɰɢɢ ɪɚɧɟɟ, ɱɟɦ ɬɟ, ɤɨɬɨɪɵɟ ɩɨɥɭɱɚɸɬ ɬɪɚɧɫɩɥɚɧɬɚɬ ɢɡ ɤɥɟɬɨɤ ɤɨɫɬɧɨɝɨ ɦɨɡɝɚ [13]. Ʉɪɨɦɟ ɬɨɝɨ, ɥɟɝɱɟ ɪɟɲɚɟɬɫɹ ɩɪɨɛɥɟɦɚ ɬɤɚɧɟɜɨɣ ɧɟɫɨɜɦɟɫɬɢɦɨɫɬɢ ɭ ɞɨɧɨɪɚ ɢ ɪɟɰɢɩɢɟɧɬɚ, ɱɟɦ ɩɪɢ ɢɫɩɨɥɶɡɨɜɚɧɢɢ ɤɨɫɬɧɨɝɨ ɦɨɡɝɚ ɢɥɢ ɩɟɪɢɮɟɪɢɱɟɫɤɨɣ ɤɪɨɜɢ [13]. ɋɭɳɟɫɬɜɭɸɬ ɢ ɧɟɞɨɫɬɚɬɤɢ ɩɪɢ ɬɪɚɧɫɩɥɚɧɬɚɰɢɢ ɩɭɩɨɜɢɧɧɨɣ ɤɪɨɜɢ, ɜɤɥɸɱɚɹ ɧɟɞɨɫɬɭɩɧɨɫɬɶ ɦɚɬɟɪɢɚɥɚ ɞɥɹ ɩɨɫɥɟɞɭɸɳɢɯ ɜɜɟɞɟɧɢɣ ɩɚɰɢɟɧɬɭ ɫɬɜɨɥɨɜɵɯ ɤɥɟɬɨɤ ɢ/ɢɥɢ ɥɢɦɮɨɰɢɬɨɜ ɨɬ ɞɨɧɨɪɚ ɩɪɢ ɧɟɭɞɚɱɧɨɣ ɬɪɚɧɫɩɥɚɧɬɚɰɢɢ ɢ ɧɢɡɤɨɟ ɤɨɥɢɱɟɫɬɜɨ ȽɋɄ ɜ ɟɞɢɧɨɦ ɨɛɪɚɡɰɟ, ɱɬɨ ɦɨɠɟɬ ɜɵɡɜɚɬɶ ɨɬɫɪɨɱɟɧɧɨɟ ɩɪɢɠɢɜɥɟɧɢɟ [13]. ɗɬɨɬ ɧɟɞɨɫɬɚɬɨɤ ɨɬɧɨɫɢɬɫɹ ɝɥɚɜɧɵɦ ɨɛɪɚɡɨɦ ɤ ɩɨɩɵɬɤɚɦ ɪɚɫɲɢɪɢɬɶ ɩɭɥ ɩɪɨɝɟɧɢɬɨɪɧɵɯ ɤɥɟɬɨɤ ɢ, ɜ ɱɚɫɬɧɨɫɬɢ, ɤ ɬ.ɧ. «ɧɚɢɜɧɵɦ» ȽɋɄ. ȼɚɠɧɟɣɲɚɹ ɯɚɪɚɤɬɟɪɢɫɬɢɤɚ ȽɋɄ – ɫɩɨɫɨɛɧɨɫɬɶ ɤ ɫɚɦɨɨɛɧɨɜɥɟɧɢɸ ɢ ɨɛɪɚɡɨɜɚɧɢɸ ɛɨɥɟɟ ɞɢɮɮɟɪɟɧɰɢɪɨɜɚɧɧɵɯ ɤɥɟɬɨɤ. ɇɟɫɦɨɬɪɹ ɧɚ ɬɨ, ɱɬɨ ɞɨɫɬɭɩɧɵ ɦɟɬɨɞɵ ɨɛɧɚɪɭɠɟɧɢɹ ȽɋɄ in vitro, ɬɚɤɢɟ, ɤɚɤ ɤɨɥɨɧɢɟɨɛɪɚɡɭɸɳɢɟ ɤɥɟɬɤɢ ɫ ɜɵɫɨɤɢɦ ɩɪɨɥɢɮɟɪɚɬɢɜɧɵɦ ɩɨɬɟɧɰɢɚɥɨɦ (HPP-CFC), ɤɥɟɬɤɢ, ɢɧɢɰɢɢɪɭɸɳɢɟ ɞɨɥɝɨɜɪɟɦɟɧɧɭɸ ɤɭɥɶɬɭɪɭ (LTCIC) ɢ ɤɥɟɬɤɢ, ɮɨɪɦɢɪɭɸɳɢɟ ɤɨɥɨɧɢɢ ɫ ɦɨɪɮɨɥɨɝɢɟɣ ɬɢɩɚ «cobblestone» (CAFC), ɞɨ ɫɢɯ ɩɨɪ ɧɟɹɫɧɨ, ɨɛɧɚɪɭɠɢɜɚɸɬ ɥɢ ɜɫɟ ɷɬɢ ɦɟɬɨɞɵ ɢɦɟɧɧɨ ɞɨɥɝɨɠɢɜɭɳɢɟ ɪɟɩɨɩɭɥɢɪɭɸɳɢɟ ȽɋɄ ɤɨɫɬɧɨɝɨ ɦɨɡɝɚ. ɋɭɳɟɫɬɜɭɸɬ ɢ ɦɟɬɨɞɵ ɩɨɞɫɱɟɬɚ ɹɞɪɨɫɨɞɟɪɠɚɳɢɯ ɤɥɟɬɨɤ, ɝɪɚɧɭɥɨɰɢɬɨɜ-ɦɚɤɪɨɮɚɝɨɜɵɯ (CFU-GM), ɷɪɢɬɪɨɢɞɧɵɯ (BFU-E) ɢ ɦɭɥɶɬɢɩɨɬɟɧɬɧɵɯ (CFU-GEMM) ɩɪɨɝɟɧɢɬɨɪɧɵɯ ɤɥɟɬɨɤ [18, 19,38,39, 54, 59, 67, 90, 99, 101]. 26 ɑɟɥɨɜɟɱɟɫɤɢɟ ȽɋɄ ɨɛɧɚɪɭɠɢɜɚɸɬɫɹ ɜ ɩɨɩɭɥɹɰɢɢ ɤɥɟɬɨɤ, ɷɤɫɩɪɟɫɫɢɪɭɸɳɢɯ ɜɵɫɨɤɢɟ ɭɪɨɜɧɢ ɚɧɬɢɝɟɧɚ CD34 ɩɪɢ ɨɬɫɭɬɫɬɜɢɢ ɚɧɬɢɝɟɧɚ CD38 (CD34+ and CD38–) [18]. Ʉɨɧɰɟɧɬɪɚɰɢɹ ȽɋɄ ɜ ɩɭɩɨɜɢɧɧɨɣ ɤɪɨɜɢ, ɤɚɤ ɛɵɥɨ ɩɨɤɚɡɚɧɨ, ɜɵɲɟ, ɱɟɦ ɜ ɤɨɫɬɧɨɦ ɦɨɡɝɟ ɜɡɪɨɫɥɵɯ ɢɥɢ ɜ ɰɢɬɨɤɢɧ-ɦɨɛɢɥɢɡɨɜɚɧɧɨɣ ɩɟɪɢɮɟɪɢɱɟɫɤɨɣ ɤɪɨɜɢ ɜɡɪɨɫɥɵɯ [18]. ɗɬɚ ɩɨɜɵɲɟɧɧɚɹ ɜɫɬɪɟɱɚɟɦɨɫɬɶ ɢ, ɜɢɞɢɦɨ, ɩɨɜɵɲɟɧɧɨɟ ɤɨɥɢɱɟɫɬɜɨ ȽɋɄ ɢɡ ɉɄ, ɩɨ ɫɪɚɜɧɟɧɢɸ ɫ ɤɥɟɬɤɚɦɢ ɤɨɫɬɧɨɝɨ ɦɨɡɝɚ, ɤɨɪɪɟɥɢɪɭɟɬ ɫ ɩɨɜɵɲɟɧɧɨɣ ɜɫɬɪɟɱɚɟɦɨɫɬɶɸ ɢ ɩɪɨɥɢɮɟɪɚɬɢɜɧɨɣ ɫɩɨɫɨɛɧɨɫɬɶɸ ɝɟɦɚɬɨɩɨɷɬɢɱɟɫɤɢɯ ɩɪɨɝɟɧɢɬɨɪɧɵɯ ɤɥɟɬɨɤ (ɤɚɤ ɨɛɧɚɪɭɠɢɜɚɸɬ CFU-GM, BFUE, CFU-GEMM) ɜ ɉɄ. ȼɢɞɢɦɨ, ɜ ɷɬɨɦ ɢ ɫɨɫɬɨɢɬ ɩɪɢɱɢɧɚ, ɩɨɱɟɦɭ ɦɚɥɵɟ ɤɨɥɢɱɟɫɬɜɚ ɫɨɛɪɚɧɧɨɣ ɉɄ (50–200 ɦɥ) ɦɨɝɭɬ ɢɦɟɬɶ ɤɥɢɧɢɱɟɫɤɭɸ ɡɧɚɱɢɦɨɫɬɶ, ɬɨɝɞɚ ɤɚɤ ɝɨɪɚɡɞɨ ɛɨɥɶɲɢɟ ɤɨɥɢɱɟɫɬɜɚ ɤɨɫɬɧɨɝɨ ɦɨɡɝɚ ɧɟɨɛɯɨɞɢɦɵ ɞɥɹ ɭɫɩɟɲɧɨɣ ɬɪɚɧɫɩɥɚɧɬɚɰɢɢ [18, 19,22,34, 38, 39, 54, 59, 67, 90, 99, 101]. ȼɵɫɨɤɚɹ ɩɥɚɫɬɢɱɧɨɫɬɶ ȽɋɄ ɢɡ ɉɄ ɛɵɥɚ ɩɪɨɞɟɦɨɧɫɬɪɢɪɨɜɚɧɚ ɩɪɢ ɢɯ ɞɢɮɮɟɪɟɧɰɢɚɰɢɢ ɜ ɤɥɟɬɤɢ ɪɚɡɧɵɯ ɬɤɚɧɟɣ, ɜɤɥɸɱɚɹ ɬɤɚɧɢ ɋɋɋ, ɱɬɨ ɹɜɥɹɟɬɫɹ ɭɤɚɡɚɧɢɟɦ ɧɚ ɩɟɪɫɩɟɤɬɢɜɵ ɢɯ ɬɟɪɚɩɜɬɢɱɟɫɤɨɝɨ ɢɫɩɨɥɶɡɨɜɚɧɢɹ. 1.3.4. ɉɪɨɬɟɨɦɢɤɚ ȽɋɄ ȼ ɬɟɱɟɧɢɟ ɩɪɟɞɲɟɫɬɜɭɸɳɢɯ ɥɟɬ ɧɚɛɥɸɞɚɥɨɫɶ ɜɨɡɪɚɫɬɚɧɢɟ ɱɢɫɥɚ ɢɫɫɥɟɞɨɜɚɧɢɣ ɋɄ ɫ ɩɨɦɨɳɶɸ ɦɟɬɨɞɨɜ ɩɪɨɬɟɨɦɢɤɢ. ȼ ɷɬɢɯ ɪɚɛɨɬɚɯ ɛɵɥɚ ɩɨɞɬɜɟɪɠɞɟɧɚ ɩɨɥɟɡɧɨɫɬɶ 2D ɞɥɹ ɪɚɡɞɟɥɟɧɢɹ ɫɥɨɠɧɵɯ ɛɟɥɤɨɜɵɯ ɫɦɟɫɟɣ ɢɡ ɫɬɜɨɥɨɜɵɯ ɤɥɟɬɨɤ ɪɚɡɧɨɝɨ ɬɢɩɚ. ȼ ɱɚɫɬɧɨɫɬɢ, ɫɨɜɦɟɫɬɧɨɟ ɢɫɩɨɥɶɡɨɜɚɧɢɟ 2D ɢ MALDI ɦɚɫɫ-ɫɩɟɤɬɪɨɦɟɬɪɢɢ ɞɥɹ ɢɞɟɧɬɢɮɢɤɚɰɢɢ ɢ ɯɚɪɚɤɬɟɪɢɫɬɢɤɢ ɛɟɥɤɨɜ ɪɚɡɧɵɯ ɋɄ ɩɪɟɞɨɫɬɚɜɢɥɨ ɡɧɚɱɢɬɟɥɶɧɵɟ ɦɚɫɫɢɜɵ ɢɧɮɨɪɦɚɰɢɢ ɨ ɦɨɥɟɤɭɥɹɪɧɵɯ ɦɟɯɚɧɢɡɦɚɯ ɪɟɝɭɥɹɰɢɢ ɋɄ. ɂ, ɱɬɨ ɟɳɟ ɛɨɥɟɟ ɜɚɠɧɨ, ɷɬɢ ɪɚɛɨɬɵ ɩɨɡɜɨɥɢɥɢ ɭɬɨɱɧɢɬɶ ɩɪɢɪɨɞɭ ɜɧɭɬɪɟɧɧɢɯ 27 ɜɡɚɢɦɨɞɟɣɫɬɜɢɣ ɦɟɠɞɭ ɪɚɡɧɵɦɢ ɫɭɛɤɥɟɬɨɱɧɵɦɢ ɫɬɪɭɤɬɭɪɚɦɢ ɢ ɨɩɪɟɞɟɥɢɬɶ ɪɨɥɶ ɛɟɥɤɨɜ ɜ ɦɨɥɟɤɭɥɹɪɧɵɯ ɩɪɟɜɪɚɳɟɧɢɹɯ, ɢɦɟɸɳɢɯ ɛɢɨɥɨɝɢɱɟɫɤɭɸ ɡɧɚɱɢɦɨɫɬɶ. ɋ ɩɨɦɨɳɶɸ ɩɪɨɬɟɨɦɢɤɢ ɜɨɡɦɨɠɧɨ ɤɚɤ ɢɡɭɱɟɧɢɟ ɨɞɧɨɣ ɤɥɟɬɨɱɧɨɣ ɩɨɩɭɥɹɰɢɢ ɩɨ ɫɪɚɜɧɟɧɢɸ ɫ ɞɪɭɝɨɣ, ɬɚɤ ɢ ɨɞɧɨɣ ɢ ɬɨɣ ɠɟ ɩɨɩɭɥɹɰɢɢ ɜ ɪɚɡɧɵɯ ɭɫɥɨɜɢɹɯ ɤɭɥɶɬɢɜɢɪɨɜɚɧɢɹ. Ɍɚɤɢɦ ɨɛɪɚɡɨɦ, ɞɨɫɬɢɝɚɟɬɫɹ ɩɨɧɢɦɚɧɢɟ ɩɨɜɟɞɟɧɢɹ ɤɨɧɤɪɟɬɧɨɣ ɩɨɩɭɥɹɰɢɢ ɋɄ, ɱɬɨ ɩɪɨɥɢɜɚɟɬ ɫɜɟɬ ɧɚ ɮɚɤɬɨɪɵ, ɜɨɜɥɟɱɟɧɧɵɟ ɜ ɤɨɧɬɪɨɥɶ ɷɬɢɯ ɭɧɢɤɚɥɶɧɵɯ ɤɥɟɬɨɤ ɢ ɨɩɪɟɞɟɥɟɧɢɟ ɢɯ ɛɢɨɥɨɝɢɱɟɫɤɨɣ ɪɨɥɢ. ȼ 2006 ɝ. Sun ɫ ɫɨɬɪɭɞɧɢɤɚɦɢ ɩɪɟɞɩɪɢɧɹɥ ɩɨɩɵɬɤɭ ɫ ɩɨɦɨɳɶɸ ɩɪɨɬɟɨɦɢɤɢ ɨɯɚɪɚɤɬɟɪɢɡɨɜɚɬɶ ɩɪɨɥɢɮɟɪɚɰɢɸ ɢ ɨɫɬɟɨɝɟɧɧɵɣ ɩɨɬɟɧɰɢɚɥ ɦɟɡɟɧɯɢɦɚɥɶɧɵɯ ɫɬɜɨɥɨɜɵɯ ɤɥɟɬɨɤ (MCK) ɜɨ ɜɪɟɦɹ ɩɚɫɫɢɪɨɜɚɧɢɹ ɢ ɢɞɟɧɬɢɮɢɰɢɪɨɜɚɬɶ ɛɟɥɤɢ, ɤɨɬɨɪɵɟ ɩɨ-ɪɚɡɧɨɦɭ ɪɟɝɭɥɢɪɭɸɬɫɹ ɜ MCK ɜɨ ɜɪɟɦɹ ɩɚɫɫɢɪɨɜɚɧɢɹ ɢ ɨɫɬɟɨɝɟɧɧɨɣ ɞɢɮɮɟɪɟɧɰɢɚɰɢɢ [82]. ɂɦ ɭɞɚɥɨɫɶ ɩɨɤɚɡɚɬɶ, ɱɬɨ ɩɪɨɥɢɮɟɪɚɰɢɹ ɢ ɨɫɬɟɨɝɟɧɧɚɹ ɫɩɨɫɨɛɧɨɫɬɶ MCK ɫɧɢɠɚɟɬɫɹ ɜɨ ɜɪɟɦɹ ɩɚɫɫɢɪɨɜɚɧɢɹ [82]. ɇɟɫɤɨɥɶɤɨ ɛɟɥɤɨɜ, ɤɚɤ ɛɵɥɨ ɨɛɧɚɪɭɠɟɧɨ, ɩɨ-ɪɚɡɧɨɦɭ ɪɟɝɭɥɢɪɭɸɬɫɹ ɜɨ ɜɪɟɦɹ ɩɚɫɫɢɪɨɜɚɧɢɹ, ɢ ɫɪɟɞɢ ɧɢɯ ɛɵɥɢ ɛɟɥɤɢ, ɫɜɹɡɚɧɧɵɟ ɫ ɤɥɟɬɨɱɧɨɣ ɩɪɨɥɢɮɟɪɚɰɢɟɣ, ɤɥɟɬɨɱɧɵɦ ɰɢɤɥɨɦ, ɦɨɪɮɨɥɨɝɢɱɟɫɤɢɦɢ ɢɡɦɟɧɟɧɢɹɦɢ, ɚɩɨɩɬɨɡɨɦ, ɩɪɢɱɟɦ ɤɨɥɢɱɟɫɬɜɨ ɷɬɢɯ ɛɟɥɤɨɜ ɫɧɢɠɚɥɨɫɶ ɜɨ ɜɪɟɦɹ ɩɚɫɫɢɪɨɜɚɧɢɹ [82]. Ɋɟɡɭɥɶɬɚɬɵ ɷɬɢɯ ɪɚɛɨɬ ɭɤɚɡɵɜɚɸɬ ɧɚ ɬɨ, ɱɬɨ ɩɨ-ɪɚɡɧɨɦɭ ɪɟɝɭɥɢɪɭɟɦɵɟ ɩɚɫɫɚɠ-ɫɩɟɰɢɮɢɱɧɵɟ ɛɟɥɤɢ ɦɨɝɭɬ ɢɝɪɚɬɶ ɨɩɪɟɞɟɥɟɧɧɭɸ ɪɨɥɶ ɜ ɫɧɢɠɟɧɢɢ ɩɨɬɟɧɰɢɚɥɚ ɨɫɬɟɨɝɟɧɧɨɣ ɞɢɮɮɟɪɟɧɰɢɚɰɢɢ ɩɪɢ ɩɚɫɫɢɪɨɜɚɧɢɢ. Ȼɨɥɟɟ ɬɨɝɨ, ɩɪɨɥɢɮɟɪɚɰɢɨɧɧɵɣ ɢ ɨɫɬɟɨɝɟɧɧɵɣ ɩɨɬɟɧɰɢɚɥ MCK ɫɭɳɟɫɬɜɟɧɧɨ ɫɧɢɠɚɥɢɫɶ ɫ ɭɜɟɥɢɱɟɧɢɟɦ ɱɢɫɥɚ ɩɚɫɫɚɠɟɣ. Ⱦɥɹ ɨɬɜɟɬɚ ɧɚ ɜɨɩɪɨɫ, ɨɬɜɟɬɫɬɜɟɧɧɚ ɥɢ ɡɚ ɫɧɢɠɟɧɢɟ ɩɪɨɥɢɮɟɪɚɰɢɨɧɧɨɝɨ ɢ ɨɫɬɟɨɝɟɧɧɨɝɨ ɩɨɬɟɧɰɢɚɥɚ ɩɪɢ ɩɚɫɫɢɪɨɜɚɧɢɢ ɷɤɫɩɪɟɫɫɢɹ ɫɩɟɰɢɮɢɱɟɫɤɢɯ ɛɟɥɤɨɜ, ɷɬɢ ɢɫɫɥɟɞɨɜɚɬɟɥɢ ɢɫɩɨɥɶɡɨɜɚɥɢ ɤɥɚɫɫɢɱɟɫɤɢɣ 28 ɩɪɨɬɟɨɦɧɵɣ ɚɧɚɥɢɡ ɞɥɹ ɩɪɨɮɢɥɢɪɨɜɚɧɢɹ ɢɡɦɟɧɟɧɢɣ ɝɥɨɛɚɥɶɧɨɣ ɛɟɥɤɨɜɨɣ ɷɤɫɩɪɟɫɫɢɢ ɜ MCK ɩɪɢ ɩɚɫɫɢɪɨɜɚɧɢɢ ɢ ɨɫɬɟɨɝɟɧɧɨɣ ɞɢɮɮɟɪɟɧɰɢɚɰɢɢ [82]. ɂɡɦɟɧɟɧɢɹ ɛɟɥɤɨɜɨɝɨ ɩɪɨɮɢɥɹ ɛɵɥɢ ɢɞɟɧɬɢɮɢɰɢɪɨɜɚɧɵ ɩɪɢ ɢɫɩɨɥɶɡɨɜɚɧɢɢ ɤɥɟɬɨɤ ɜ ɪɚɡɧɵɯ ɩɚɫɫɚɠɚɯ ɢɥɢ ɜ ɪɚɡɧɵɟ ɦɨɦɟɧɬɵ ɨɫɬɟɨɝɟɧɧɨɣ ɞɢɮɮɟɪɟɧɰɢɚɰɢɢ. ȼɫɟɝɨ ɨɤɨɥɨ 100 ɧɨɪɦɚɥɢɡɨɜɚɧɧɵɯ ɛɟɥɤɨɜɵɯ ɩɹɬɟɧ, ɤɨɬɨɪɵɟ ɧɟ ɢɡɦɟɧɢɥɢɫɶ ɜ ɪɚɡɧɵɟ ɦɨɦɟɧɬɵ ɜɪɟɦɟɧɢ, ɛɵɥɢ ɨɬɨɛɪɚɧɵ ɞɥɹ MALDI-ɚɧɚɥɢɡɚ ɞɥɹ ɨɛɟɫɩɟɱɟɧɢɹ ɤɨɧɬɪɨɥɹ (ɫɬɚɧɞɚɪɬɚ ɫɪɚɜɧɟɧɢɹ). ɂɫɩɨɥɶɡɨɜɚɧɢɟ ɤɥɚɫɫɢɱɟɫɤɨɝɨ ɢɧɫɬɪɭɦɟɧɬɚɪɢɹ ɩɪɨɬɟɨɦɢɤɢ (2D ɢ ɢɞɟɧɬɢɮɢɤɚɰɢɹ ɫ ɩɨɦɨɳɶɸ MALDI-ɫɩɟɤɬɪɨɫɤɨɩɢɢ) ɭɤɚɡɚɥɨ ɧɚ ɧɟɫɤɨɥɶɤɨ ɛɟɥɤɨɜ, ɤɨɬɨɪɵɟ, ɜɨɡɦɨɠɧɨ, ɩɪɢɱɚɫɬɧɵ ɩɪɹɦɨ ɢɥɢ ɤɨɫɜɟɧɧɨ ɤ ɤɥɟɬɨɱɧɨɦɭ ɪɨɫɬɭ ɢ ɦɭɥɶɬɢɩɨɬɟɧɰɢɢ. ɋɨɡɞɚɧɢɟ 2D-ɪɟɮɟɪɟɧɫɧɨɣ ɤɚɪɬɵ ɛɭɞɟɬ ɫɩɨɫɨɛɫɬɜɨɜɚɬɶ ɨɛɧɚɪɭɠɟɧɢɸ ɤɨɥɢɱɟɫɬɜɟɧɧɵɯ ɢ ɤɚɱɟɫɬɜɟɧɧɵɯ ɢɡɦɟɧɟɧɢɣ ɜ ɛɟɥɤɨɜɨɣ ɷɤɫɩɪɟɫɫɢɢ ɜ ɨɬɜɟɬ ɧɚ ɫɟɪɢɚɥɶɧɨɟ ɫɭɛɤɭɥɶɬɢɜɢɪɨɜɚɧɢɟ ɢ ɨɫɬɟɨɝɟɧɧɭɸ ɞɢɮɮɟɪɟɧɰɢɚɰɢɸ MCK. ȼ 2007 ɝ. Roubelakis ɫ ɫɨɬɪɭɞɧɢɤɚɦɢ ɢɫɩɨɥɶɡɨɜɚɥ 2D ɢ MALDIɦɚɫɫ-ɫɩɟɤɬɪɨɦɟɬɪɢɸ ɞɥɹ ɩɨɥɭɱɟɧɢɹ ɛɟɥɤɨɜɨɣ ɤɚɪɬɵ ɤɭɥɶɬɢɜɢɪɨɜɚɧɧɵɯ ɆɋɄ ɢɡ ɚɦɧɢɨɬɢɱɟɫɤɨɣ ɠɢɞɤɨɫɬɢ ɜɬɨɪɨɝɨ ɬɪɢɦɟɫɬɪɚ (Aɀ) ɢ ɫɪɚɜɧɢɥ ɟɟ ɫ ɤɭɥɶɬɢɜɢɪɨɜɚɧɧɵɦɢ MɋɄ ɢɡ ɤɨɫɬɧɨɝɨ ɦɨɡɝɚ [74]. Ⱦɥɹ 261 ɢɞɟɧɬɢɮɢɰɢɪɨɜɚɧɧɨɝɨ ɛɟɥɤɚ ɮɭɧɤɰɢɨɧɚɥɶɧɵɟ ɩɪɨɮɢɥɢ ɛɟɥɤɨɜ ɢɡ ɞɜɭɯ ɷɬɢɯ ɢɫɬɨɱɧɢɤɨɜ ɛɵɥɢ ɚɧɚɥɨɝɢɱɧɵ. Ɉɞɧɚɤɨ, ɤɭɥɶɬɢɜɢɪɨɜɚɧɧɵɟ Aɀ-ɆɋɄ ɨɛɧɚɪɭɠɢɥɢ ɧɟɫɤɨɥɶɤɨ ɭɧɢɤɚɥɶɧɵɯ ɛɟɥɤɨɜ, ɫɜɹɡɚɧɧɵɯ ɫ ɩɪɨɥɢɮɟɪɚɰɢɟɣ ɢ ɩɪɢɦɢɬɢɜɧɵɦ ɮɟɧɨɬɢɩɨɦ, ɤɨɬɨɪɵɟ ɦɨɝɭɬ ɩɪɨɹɜɥɹɬɶ ɱɟɬɤɢɟ ɫɜɨɣɫɬɜɚ ɞɜɭɯ ɬɢɩɨɜ ɤɥɟɬɨɤ. ɉɪɢɧɢɦɚɹ ɜɨ ɜɧɢɦɚɧɢɟ ɥɟɝɤɭɸ ɞɨɫɬɭɩɧɨɫɬɶ ɷɬɨɝɨ ɧɨɜɨɝɨ ɢɫɬɨɱɧɢɤɚ ɤɥɟɬɨɤ ɢ ɜɨɡɦɨɠɧɨɫɬɶ ɪɚɡɦɧɨɠɟɧɢɹ ɆɋɄ ɞɥɹ ɢɫɫɥɟɞɨɜɚɧɢɹ ɋɄ, Aɀ ɹɜɥɹɟɬɫɹ ɨɬɥɢɱɧɵɦ ɩɨɫɬɚɜɳɢɤɨɦ ɆɋɄ ɤɚɤ ɞɥɹ ɷɤɫɩɟɪɢɦɟɧɬɨɜ, ɬɚɤ ɢ ɞɥɹ ɬɟɪɚɩɢɢ [74]. ɉɪɢɦɟɪɨɦ ɛɟɥɤɚ, ɨɛɧɚɪɭɠɟɧɧɨɝɨ ɜ ɤɭɥɶɬɢɜɢɪɨɜɚɧɧɵɯ Aɀ-ɆɋɄ ɢ ɆɋɄ ɢɡ ɤɨɫɬɧɨɝɨ 29 ɦɨɡɝɚ, ɹɜɥɹɟɬɫɹ ɜɢɦɟɧɬɢɧ, ɤɨɬɨɪɵɣ ɩɪɟɞɫɬɚɜɥɹɟɬ ɫɨɛɨɣ ɝɥɚɜɧɵɣ ɮɢɥɚɦɟɧɬɧɵɣ ɛɟɥɨɤ-ɢɧɬɟɪɦɟɞɢɚɬɨɪ ɜ ɆɋɄ ɢ ɱɚɫɬɨ ɢɫɩɨɥɶɡɭɟɬɫɹ ɤɚɤ ɦɚɪɤɟɪ ɪɚɡɜɢɬɢɹ ɤɥɟɬɨɤ ɢ ɬɤɚɧɟɣ [41,69]. Ȼɵɥɨ ɬɚɤɠɟ ɩɨɤɚɡɚɧɨ, ɱɬɨ ɜɢɦɟɧɬɢɧ ɭɱɚɫɬɜɭɟɬ ɜ ɪɹɞɟ ɤɪɢɬɢɱɟɫɤɢɯ ɞɟɣɫɬɜɢɣ, ɫɜɹɡɚɧɧɵɯ ɫ ɨɪɝɚɧɢɡɚɰɢɟɣ ɛɟɥɤɨɜ, ɤɨɬɨɪɵɟ ɜɨɜɥɟɱɟɧɵ ɜ ɚɞɝɟɡɢɸ ɢ ɪɟɝɭɥɢɪɭɸɬ ɮɭɧɤɰɢɢ ɢɧɬɟɝɪɢɧɚ, ɦɢɝɪɚɰɢɸ ɢ ɤɥɟɬɨɱɧɭɸ ɫɢɝɧɚɥɢɡɚɰɢɸ. ȼ ɷɬɨɣ ɫɜɹɡɢ ɜɢɦɟɧɬɢɧ ɫɱɢɬɚɟɬɫɹ ɤɥɸɱɟɜɨɣ ɦɨɥɟɤɭɥɨɣ ɜ ɮɢɡɢɨɥɨɝɢɱɟɫɤɢɯ ɩɪɨɰɟɫɫɚɯ, ɬɚɤɢɯ, ɤɚɤ ɤɥɟɬɨɱɧɵɣ ɝɨɦɟɨɫɬɚɡ, ɚɩɨɩɬɨɡ, ɰɟɥɨɫɬɧɨɫɬɶ ɷɧɞɨɬɟɥɢɹ ɢ ɩɨɜɪɟɠɞɟɧɢɟ ɧɟɪɜɚ [41,69]. Ⱦɪɭɝɢɦ ɩɪɢɦɟɪɨɦ ɹɜɥɹɟɬɫɹ ɝɚɥɟɫɬɢɧ-1, ɜɚɠɧɚɹ ɦɨɥɟɤɭɥɚ ɪɟɝɭɥɹɰɢɢ ɋɄ, ɨɛɧɚɪɭɠɟɧɧɚɹ ɧɚ ɤɥɟɬɨɱɧɨɣ ɩɨɜɟɪɯɧɨɫɬɢ ɆɋɄ [44], ɭɱɚɫɬɜɭɸɳɚɹ ɜ ɜɧɟɤɥɟɬɨɱɧɵɯ ɜɡɚɢɦɨɞɟɣɫɬɜɢɹɯ ɦɚɬɪɢɤɫ-ɤɥɟɬɤɚ ɢ ɪɟɝɭɥɢɪɭɸɳɚɹ ɤɥɟɬɨɱɧɭɸ ɞɢɮɮɟɪɟɧɰɢɚɰɢɸ ɫɬɜɨɥɨɜɵɯ ɤɥɟɬɨɤ, ɩɪɨɥɢɮɟɪɚɰɢɸ ɢ ɚɩɨɩɬɨɡ ɡɚ ɫɱɟɬ ɜɡɚɢɦɨɞɟɣɫɬɜɢɹ ɫ ɜɧɟɤɥɟɬɨɱɧɵɦ ɦɚɬɪɢɤɫɨɦ ɢ ɢɦɦɭɧɧɨɣ ɫɢɫɬɟɦɨɣ [13,25]. Ɍɪɚɧɫɞɭɰɢɧ-ɩɨɞɨɛɧɵɣ ɛɟɥɨɤ-ɭɫɢɥɢɬɟɥɶ 3, ɨɛɧɚɪɭɠɟɧɧɵɣ ɜ ɤɭɥɶɬɢɜɢɪɨɜɚɧɧɵɯ ɆɋɄ ɢɡ ɨɛɨɢɯ ɢɫɬɨɱɧɢɤɨɜ, ɹɜɥɹɟɬɫɹ ɭɱɚɫɬɧɢɤɨɦ Wnt-ɩɭɬɢ ɩɟɪɟɞɚɱɢ ɫɢɝɧɚɥɚ, ɜɥɢɹɸɳɟɝɨ ɧɚ ɪɨɫɬ ɢ ɪɚɡɜɢɬɢɟ ɢ, ɬɚɤɢɦ ɨɛɪɚɡɨɦ, ɨɩɪɟɞɟɥɹɸɳɟɝɨ ɫɭɞɶɛɭ ɤɥɟɬɨɤ [21]. ȼ 2009 ɝ. Mareddy ɫ ɫɨɬɪɭɞɧɢɤɚɦɢ [61] ɢɫɩɨɥɶɡɨɜɚɥ ɩɪɨɬɟɨɦɢɤɭ ɞɥɹ ɢɡɭɱɟɧɢɹ ɦɨɥɟɤɭɥɹɪɧɵɯ ɦɟɯɚɧɢɡɦɨɜ, ɭɩɪɚɜɥɹɸɳɢɯ ɫɚɦɨɨɛɧɨɜɥɟɧɢɟɦ ɢ ɞɢɮɮɟɪɟɧɰɢɚɰɢɟɣ ɆɋɄ. ɐɟɥɶɸ ɷɬɨɝɨ ɢɫɫɥɟɞɨɜɚɧɢɹ ɛɵɥɨ ɫɨɡɞɚɧɢɟ ɩɨɥɧɨɣ ɩɪɨɬɟɨɦɧɨɣ ɪɟɮɟɪɟɧɫ-ɤɚɪɬɵ ɆɋɄ ɢɡ ɤɨɫɬɧɨɝɨ ɦɨɡɝɚ (ɆɋɄ-ɄɆ), ɤɨɬɨɪɚɹ ɩɨɦɨɝɥɚ ɛɵ ɥɭɱɲɟ ɩɨɧɹɬɶ ɜɧɭɬɪɟɧɧɢɟ ɦɟɯɚɧɢɡɦɵ ɫɚɦɨɨɛɧɨɜɥɟɧɢɹ ɢ ɞɢɮɮɟɪɟɧɰɢɚɰɢɢ ɆɋɄ-ɄɆ. Ȼɟɥɤɨɜɵɣ ɩɪɨɮɢɥɶ ɤɥɨɧɚɥɶɧɵɯ ɩɨɩɭɥɹɰɢɣ ɆɋɄ ɛɵɥ ɢɡɭɱɟɧ ɫ ɩɨɦɨɳɶɸ ɞɜɭɦɟɪɧɨɣ ɠɢɞɤɨɫɬɧɨɣ ɯɪɨɦɚɬɨɝɪɚɮɢɢ/MALDI-ɦɚɫɫ-ɫɩɟɤɬɪɨɦɟɬɪɢɢ ɢ ɫɢɫɬɟɦɵ MASCOT (Matrix Science) ɞɥɹ ɞɟɤɨɧɜɨɥɸɬɧɨɣ ɨɛɪɚɛɨɬɤɢ ɦɚɫɫɫɩɟɤɬɪɨɜ ɢ ɩɨɥɭɱɟɧɢɹ ɜɟɪɨɹɬɧɨɫɬɧɵɯ ɯɚɪɚɤɬɟɪɢɫɬɢɤ ɞɥɹ ɤɚɠɞɨɝɨ ɢɡ 30 ɨɛɪɚɡɰɨɜ [61]. ȼɫɟɝɨ ɛɵɥɨ ɢɞɟɧɬɢɮɢɰɢɪɨɜɚɧɨ 83 ɛɟɥɤɚ, ɜɤɥɸɱɚɹ ɫɬɪɭɤɬɭɪɧɵɟ ɢ ɰɢɬɨɫɤɟɥɟɬɧɵɟ, ɤɚɥɶɰɢɣ-ɫɜɹɡɵɜɚɸɳɢɟ, ɰɢɬɨɤɢɧɟɬɢɱɟɫɤɢɟ, ɚ ɬɚɤɠɟ ɩɪɟɞɫɬɚɜɢɬɟɥɟɣ ɫɟɦɟɣɫɬɜɚ ɮɢɥɚɦɟɧɬɨɜ-ɢɧɬɟɪɦɟɞɢɚɬɨɪɨɜ. ȼ 2007 ɝ. Seshi ɫ ɫɨɬɪɭɞɧɢɤɚɦɢ ɩɪɟɞɫɬɚɜɢɥ ɧɨɜɵɣ 2D ɩɪɨɬɨɤɨɥ, ɜ ɫɨɨɬɜɟɬɫɬɜɢɢ ɫ ɤɨɬɨɪɵɦ ɨɛɪɚɡɰɵ ɛɟɥɤɨɜ ɢɡ ɧɨɪɦɚɥɶɧɵɯ ɢ ɪɚɤɨɜɵɯ ɦɟɡɟɧɯɢɦɚɥɶɧɵɯ ɩɪɨɝɟɧɢɬɨɪɧɵɯ ɤɥɟɬɨɤ ɤɨɫɬɧɨɝɨ ɦɨɡɝɚ ɱɟɥɨɜɟɤɚ ɛɵɥɢ ɢɫɩɨɥɶɡɨɜɚɧɵ ɤɚɤ ɦɨɞɟɥɶ ɞɥɹ ɧɨɜɨɣ ɤɨɦɛɢɧɚɰɢɢ ɠɢɞɤɨɮɚɡɧɨɝɨ ɢɡɨɷɥɟɤɬɪɢɱɟɫɤɨɝɨ ɮɨɤɭɫɢɪɨɜɚɧɢɹ (ɂɗɎ) ɫ 2D [78]. ɉɪɟɞɜɚɪɢɬɟɥɶɧɨɟ ɮɪɚɤɰɢɨɧɢɪɨɜɚɧɢɟ ɬɚɤɢɦ ɫɩɨɫɨɛɨɦ ɩɨɡɜɨɥɢɥɨ ɩɨɥɭɱɢɬɶ ɩɹɬɶ ɫɥɟɞɭɸɳɢɯ ɩɨɞɮɪɚɤɰɢɣ: ɮɪɚɤɰɢɹ 1 (pI 3,0–4,6), ɮɪɚɤɰɢɹ 2 (pI 4,6–5,4), ɮɪɚɤɰɢɹ 3 (pI 5,4–6,2), ɮɪɚɤɰɢɹ 4 (pI 6,2–7,0), ɮɪɚɤɰɢɹ 5 (pI 7,0–10,0) [67]. ɉɪɢ ɷɬɢɯ ɭɫɥɨɜɢɹɯ 2D ɜɵɹɜɢɥ 5000 ɛɟɥɨɤ-ɫɨɞɟɪɠɚɳɢɯ ɩɹɬɟɧ ɜ ɞɢɚɩɚɡɨɧɟ ɪɇ 4,6–7,0. ɂɡɛɢɪɚɬɟɥɶɧɨɟ ɧɚɧɟɫɟɧɢɟ ɦɟɬɤɢ ɜ ɤɨɦɛɢɧɚɰɢɢ ɫ ɩɨɫɥɟɞɭɸɳɢɦ MALDI ɩɨɡɜɨɥɢɥɨ ɢɞɟɧɬɢɮɢɰɢɪɨɜɚɬɶ ɛɟɥɤɢ, ɷɤɫɩɪɟɫɫɢɪɭɟɦɵɟ ɪɚɤɨɜɵɦɢ ɤɥɟɬɤɚɦɢ. 72 ɢɡ ɷɬɢɯ ɛɟɥɤɨɜ (56%) ɷɤɫɩɪɟɫɫɢɪɨɜɚɥɢɫɶ ɜ 1,25 ɪɚɡɚ ɚɤɬɢɜɧɟɟ ɢɥɢ ɜ ɬɚɤɨɣ ɠɟ ɫɬɟɩɟɧɢ ɩɨɞɚɜɥɹɥɢɫɶ ɜ ɪɚɤɨɜɵɯ ɤɥɟɬɤɚɯ ɩɨ ɫɪɚɜɧɟɧɢɸ ɫ ɧɨɪɦɚɥɶɧɵɦɢ. ɉɨɥɭɱɟɧɧɵɟ ɞɚɧɧɵɟ ɨɛɫɭɠɞɚɥɢɫɶ ɜ ɫɜɹɡɢ ɫ ɢɡɦɟɧɟɧɢɟɦ ɛɢɨɥɨɝɢɱɟɫɤɢɯ ɩɪɨɰɟɫɫɨɜ ɜ ɦɟɡɟɧɯɢɦɚɥɶɧɵɯ ɩɪɨɝɟɧɢɬɨɪɧɵɯ ɤɥɟɬɤɚɯ, ɩɨɪɚɠɟɧɧɵɯ ɥɟɣɤɟɦɢɟɣ. ȼ ɱɚɫɬɧɨɫɬɢ, ɜɵɹɫɧɢɥɨɫɶ, ɱɬɨ ɪɹɞ ɰɢɬɨɫɬɪɭɤɬɭɪɧɵɯ ɛɟɥɤɨɜ ɢɡɛɢɪɚɬɟɥɶɧɨ ɪɟɝɭɥɢɪɭɟɬɫɹ ɜ ɪɚɤɨɜɵɯ ɤɥɟɬɤɚɯ [78]. ɂɫɩɨɥɶɡɨɜɚɧɢɟ ɜɵɲɟɨɩɢɫɚɧɧɨɝɨ ɩɪɢɟɦɚ ɮɪɚɤɰɢɨɧɢɪɨɜɚɧɢɹ ɜɫɟ ɱɚɳɟ ɧɚɛɥɸɞɚɟɬɫɹ ɜ ɩɪɨɬɟɨɦɢɤɟ, ɨɞɧɚɤɨ, ɧɟɫɦɨɬɪɹ ɧɚ ɟɝɨ ɜɵɫɨɤɭɸ ɪɚɡɪɟɲɚɸɳɭɸ ɫɩɨɫɨɛɧɨɫɬɶ, ɧɟ ɫɬɚɥɨ ɲɢɪɨɤɨ ɪɚɫɩɪɨɫɬɪɚɧɟɧɧɵɦ. Ɏɪɚɤɰɢɨɧɢɪɨɜɚɧɢɟ ɨɛɪɚɡɰɨɜ, ɤ ɬɨɦɭ ɠɟ, ɦɨɠɟɬ ɩɪɢɜɨɞɢɬɶ ɤ ɩɨɬɟɪɟ ɛɟɥɤɨɜ ɢɥɢ ɪɚɡɞɟɥɟɧɢɸ ɤɚɤɨɝɨ-ɥɢɛɨ ɛɟɥɤɚ ɦɟɠɞɭ ɞɜɭɦɹ ɮɪɚɤɰɢɹɦɢ, ɱɬɨ ɡɚɬɪɭɞɧɹɟɬ ɢɯ ɤɨɥɢɱɟɫɬɜɟɧɧɭɸ ɨɰɟɧɤɭ. ɗɬɨ ɨɝɪɚɧɢɱɟɧɢɟ ɨɫɨɛɟɧɧɨ 31 ɭɦɟɫɬɧɨ ɩɪɢɧɹɬɶ ɜɨ ɜɧɢɦɚɧɢɟ ɩɪɢ ɫɪɚɜɧɢɬɟɥɶɧɵɯ ɢɫɫɥɟɞɨɜɚɧɢɹɯ ɛɟɥɤɨɜ. Ɍɟɦ ɧɟ ɦɟɧɟɟ, ɩɪɨɬɟɨɦɧɵɟ ɷɤɫɩɟɪɢɦɟɧɬɵ ɜ ɰɟɥɹɯ ɫɨɡɞɚɧɢɹ ɩɨɥɧɨɣ ɛɟɥɤɨɜɨɣ ɤɚɪɬɵ ɬɪɟɛɭɸɬ ɩɨɜɵɲɟɧɧɨɣ ɪɚɡɪɟɲɚɸɳɟɣ ɫɩɨɫɨɛɧɨɫɬɢ ɦɟɬɨɞɨɜ ɞɚɠɟ ɫ ɭɱɟɬɨɦ ɭɤɚɡɚɧɧɵɯ ɧɟɞɨɫɬɚɬɤɨɜ. ɉɨɩɵɬɤɢ ɨɰɟɧɢɬɶ ɩɪɨɬɟɨɦɢɤɭ ȽɋɄ ɢ ɝɟɦɨɩɨɷɬɢɱɟɫɤɢɯ ɩɪɨɝɟɧɢɬɨɪɧɵɯ ɤɥɟɬɨɤ (ȽɉɄ) ɞɨɥɠɧɵ ɞɨɩɨɥɧɹɬɶ ɪɟɡɭɥɶɬɚɬɵ ɢɫɫɥɟɞɨɜɚɧɢɣ ɷɬɢɯ ɨɛɴɟɤɬɨɜ ɦɟɬɨɞɚɦɢ ɝɟɧɨɦɢɤɢ. Tao ɫ ɫɨɬɪɭɞɧɢɤɚɦɢ ɢɫɩɨɥɶɡɨɜɚɥ ɩɪɨɬɟɨɦɢɤɭ ɞɥɹ ɫɪɚɜɧɟɧɢɹ ɱɟɥɨɜɟɱɟɫɤɢɯ CD34+ ɤɥɟɬɨɤ ɢɡ ɩɭɩɨɜɢɧɧɨɣ ɤɪɨɜɢ ɫɨ ɡɪɟɥɵɦɢ CD15+ ɦɢɟɥɨɢɞɧɵɦɢ ɤɥɟɬɤɚɦɢ [86]. Ȼɵɥɨ ɨɛɧɚɪɭɠɟɧɨ, ɱɬɨ CD34+ ɤɥɟɬɤɢ ɢɦɟɸɬ ɨɬɧɨɫɢɬɟɥɶɧɨ ɛɨɥɟɟ ɜɵɫɨɤɭɸ ɤɨɧɰɟɧɬɪɚɰɢɸ ɹɞɟɪɧɵɯ ɛɟɥɤɨɜ, ɱɟɦ ɡɪɟɥɵɟ ɤɥɟɬɤɢ. Ȼɟɥɤɢ ɬɟɩɥɨɜɨɝɨ ɲɨɤɚ ɢ ɲɚɩɟɪɨɧɵ, ɚ ɬɚɤɠɟ ɛɟɥɤɢ, ɜɚɠɧɵɟ ɞɥɹ ɦɟɠɤɥɟɬɨɱɧɨɝɨ ɩɟɪɟɧɨɫɚ, ɞɨɦɢɧɢɪɨɜɚɥɢ ɜ CD34+ ɤɥɟɬɤɚɯ, ɚ ɧɟ ɜ CD15+ ɤɥɟɬɤɚɯ. 8 ɧɨɜɵɯ ɛɟɥɤɨɜ, ɨɛɥɚɞɚɸɳɢɯ ɧɨɜɵɦɢ ɮɭɧɤɰɢɹɦɢ, ɬɚɤɠɟ ɛɵɥɨ ɢɞɟɧɬɢɮɢɰɢɪɨɜɚɧɨ. Ɉɬɦɟɬɢɦ, ɱɬɨ ɩɪɢ ɚɧɚɥɢɡɟ ɢɧɮɨɪɦɚɰɢɢ, ɩɨɥɭɱɟɧɧɨɣ ɫ ɩɨɦɨɳɶɸ ɝɟɧɨɦɢɤɢ ɢ ɩɪɨɬɟɨɦɢɤɢ ɧɚ ɤɥɟɬɤɚɯ ɱɟɥɨɜɟɤɚ, ɫɥɟɞɭɟɬ ɭɱɢɬɵɜɚɬɶ, ɱɬɨ ɩɨɩɭɥɹɰɢɢ ɬɚɤɢɯ ɤɥɟɬɨɤ ɧɟ ɨɛɧɚɪɭɠɢɜɚɸɬ ɪɚɡɥɢɱɢɣ ɜ ɤɚɪɬɢɧɚɯ ɷɤɫɩɪɟɫɫɢɢ ɦɟɠɞɭ ȽɋɄ ɢ ȽɉɄ [86]. Ɍɨɥɶɤɨ ɦɟɧɶɲɢɧɫɬɜɨ CD34+ ɤɥɟɬɨɤ ɭɞɨɜɥɟɬɜɨɪɹɟɬ ɮɭɧɤɰɢɨɧɚɥɶɧɵɦ ɤɪɢɬɟɪɢɹɦ ȽɋɄ. Ⱦɚɠɟ ɩɨɩɭɥɹɰɢɹ CD34+CD38– ɤɥɟɬɨɤ ɜɤɥɸɱɚɟɬ ɜ ɫɟɛɹ ɬɨɥɶɤɨ ɧɟɡɧɚɱɢɬɟɥɶɧɭɸ ɱɚɫɬɶ ɞɨɥɝɨɜɪɟɦɟɧɧɨ ɪɟɩɨɩɭɥɢɪɭɸɳɢɯ ȽɋɄ ɢɡ ɤɨɫɬɧɨɝɨ ɦɨɡɝɚ [86]. ȿɫɥɢ ɦɵ ɯɨɬɢɦ ɥɭɱɲɟ ɪɚɫɩɨɡɧɚɜɚɬɶ ɮɟɧɨɬɢɩɵ ɤɥɟɬɨɤ ɱɟɥɨɜɟɤɚ ɞɥɹ ɪɚɡɝɪɚɧɢɱɟɧɢɹ ȽɋɄ ɢ ȽɉɄ, ɢɧɮɨɪɦɚɰɢɹ, ɩɨɥɭɱɟɧɧɚɹ ɫ ɩɨɦɨɳɶɸ ɝɟɧɨɦɢɤɢ ɢ ɩɪɨɬɟɨɦɢɤɢ, ɛɭɞɟɬ ɤɪɚɣɧɟ ɧɟɨɛɯɨɞɢɦɚ. Ⱥ ɞɥɹ ɢɫɩɨɥɶɡɨɜɚɧɢɹ ɭɠɟ ɢɦɟɸɳɟɣɫɹ ɢɧɮɨɪɦɚɰɢɢ ɷɬɢɯ ɧɚɭɤ ɢɞɟɧɬɢɮɢɰɢɪɨɜɚɧɧɵɟ ɝɟɧɵ ɢ ɛɟɥɤɢ ɞɨɥɠɧɵ ɛɵɬɶ ɩɪɨɬɟɫɬɢɪɨɜɚɧɵ ɜ ɮɭɧɤɰɢɨɧɚɥɶɧɵɯ ɢɫɫɥɟɞɨɜɚɧɢɹɯ ȽɋɄ (ɧɚɩɪɢɦɟɪ, ɤɨɥɨɧɢɟɨɛɪɚɡɭɸɳɢɟ ɟɞɢɧɢɰɵ ɜɵɫɨɤɨɝɨ ɩɪɨɥɢɮɟɪɚɬɢɜɧɨɝɨ ɩɨɬɟɧɰɢɚɥɚ – HPP-CFC) ɢ ȽɉɄ 32 (ɫɨɞɟɪɠɚɧɢɟ ɜ ɤɪɨɜɢ ɧɚɢɛɨɥɟɟ ɩɪɢɦɢɬɢɜɧɵɯ ɩɪɟɞɲɟɫɬɜɟɧɧɢɤɨɜ ɝɟɦɨɩɨɷɡɚ LTC-IC – long-term culture-initiating cells ɢ ɤɥɟɬɨɤ, ɨɛɪɚɡɭɸɳɢɯ ɨɛɥɚɫɬɢ ɛɭɥɵɠɧɢɤɚ – CAFC) [86]. ɂɡɭɱɟɧɢɟ ɩɨɜɵɲɟɧɧɨɣ ɢɥɢ ɫɧɢɠɟɧɧɨɣ ɷɤɫɩɪɟɫɫɢɢ ɩɪɨɞɭɤɰɢɢ ɢɞɟɧɬɢɮɢɰɢɪɨɜɚɧɧɵɯ ɝɟɧɨɜ ɩɪɨɞɨɥɠɚɟɬɫɹ ɜ ɪɹɞɟ ɥɚɛɨɪɚɬɨɪɢɣ ɢ ɞɨɥɠɧɨ ɩɪɢɜɟɫɬɢ ɤ ɥɭɱɲɟɦɭ ɩɨɧɢɦɚɧɢɸ ɤɚɤ ɮɭɧɤɰɢɣ ɷɬɢɯ ɝɟɧɨɜ, ɬɚɤ ɢ ɢɯ ɫɨɨɬɜɟɬɫɬɜɭɸɳɢɯ ɩɪɨɞɭɤɬɨɜ. ɉɨɫɥɟ ɭɬɨɱɧɟɧɢɹ ɮɭɧɤɰɢɣ ɷɬɢɯ ɷɤɫɩɪɟɫɫɢɪɭɸɳɢɯ ɝɟɧɨɜ, ɩɪɨɮɢɥɢɪɨɜɚɧɢɟ ɝɟɧɨɜ ɫɬɚɧɟɬ ɛɨɥɟɟ ɡɧɚɱɢɦɵɦ. ɉɨɥɧɨɟ ɤɚɪɬɢɪɨɜɚɧɢɟ ɫɨɨɬɜɟɬɫɬɜɭɸɳɢɯ ɝɟɧɧɵɯ ɢ ɛɟɥɤɨɜɵɯ ɤɚɪɬ ɞɨɥɠɧɨ, ɜ ɫɜɨɸ ɨɱɟɪɟɞɶ, ɩɨɦɨɱɶ ɜ ɨɰɟɧɤɟ ɦɨɥɟɤɭɥɹɪɧɵɯ ɩɭɬɟɣ ɫɢɝɧɚɥɢɡɚɰɢɢ, ɚɫɫɨɰɢɢɪɨɜɚɧɧɵɯ ɫ ɪɚɡɧɵɦɢ ɧɚɛɨɪɚɦɢ ɩɨɩɭɥɹɰɢɢ ȽɋɄ. Ⱦɨɩɨɥɧɹɬ ɷɬɢ ɢɫɫɥɟɞɨɜɚɧɢɹ ɧɚɛɥɸɞɟɧɢɹ ɡɚ ɩɪɨɬɟɨɦɧɵɦɢ ɤɨɦɩɨɧɟɧɬɚɦɢ ɤɥɟɬɨɤ, ɫ ɢɫɩɨɥɶɡɨɜɚɧɢɟɦ ɩɪɟɞɥɨɠɟɧɧɵɯ ɷɬɚɥɨɧɧɵɯ ɬɨɱɟɤ ɫɪɚɜɧɟɧɢɹ. Ⱦɥɹ ɭɫɤɨɪɟɧɢɹ ɬɚɤɢɯ ɪɚɛɨɬ ɜɚɠɧɨ ɢɦɟɬɶ ɧɟɤɭɸ ɫɬɚɪɬɨɜɭɸ ɩɥɚɬɮɨɪɦɭ, ɫ ɟɞɢɧɨɨɛɪɚɡɧɵɦɢ ɷɤɫɩɟɪɢɦɟɧɬɚɥɶɧɵɦɢ ɩɪɨɰɟɞɭɪɚɦɢ, ɨɛɳɟɩɪɢɧɹɬɵɦɢ ɧɚɭɱɧɵɦ ɫɨɨɛɳɟɫɬɜɨɦ. 33 34 2. ɆȺɌȿɊɂȺɅɕ ɂ ɆȿɌɈȾɕ 2.1. Ʉɥɟɬɨɱɧɵɟ ɥɢɧɢɢ Ɉɫɬɟɨɫɚɪɤɨɦɚ ɱɟɥɨɜɟɤɚ ɤɥɟɬɨɱɧɨɣ ɥɢɧɢɢ MG63 ɛɵɥɚ ɢɫɩɨɥɶɡɨɜɚɧɚ ɜ ɤɚɱɟɫɬɜɟ ɦɨɞɟɥɶɧɨɣ ɫɢɫɬɟɦɵ ɞɥɹ ɩɪɨɬɟɨɦɧɵɯ ɢɫɫɥɟɞɨɜɚɧɢɣ ɨɫɬɟɨɛɥɚɫɬɨɜ. Ⱥɤɬɢɜɢɪɨɜɚɧɧɚɹ ɮɥɭɨɪɟɫɰɟɧɰɢɟɣ ɫɨɪɬɢɪɨɜɤɚ ɤɥɟɬɨɤ (FACS) ɛɵɥɚ ɢɫɩɨɥɶɡɨɜɚɧɚ ɞɥɹ ɤɨɧɬɪɨɥɹ ɫɨɞɟɪɠɚɧɢɹ ȾɇɄ ɫ ɰɟɥɶɸ ɨɩɪɟɞɟɥɟɧɢɹ ɫɬɟɩɟɧɢ G0/G1 ɫɢɧɯɪɨɧɢɡɚɰɢɢ ɜ ɤɥɟɬɨɱɧɨɣ ɩɨɩɭɥɹɰɢɢ. ɗɬɨ ɧɟɨɛɯɨɞɢɦɨ ɞɥɹ ɩɨɞɬɜɟɪɠɞɟɧɢɹ ɬɨɝɨ, ɱɬɨ ɧɚɛɥɸɞɚɟɦɵɟ ɦɨɥɟɤɭɥɹɪɧɵɟ ɢɡɦɟɧɟɧɢɹ ɜɵɡɜɚɧɵ ɭɫɥɨɜɢɹɦɢ ɷɤɫɩɟɪɢɦɟɧɬɚ, ɚ ɧɟ ɪɚɡɥɢɱɢɹɦɢ ɦɟɠɞɭ ɤɥɟɬɤɚɦɢ, ɧɚɯɨɞɹɳɢɦɢɫɹ ɧɚ ɪɚɡɧɵɯ ɫɬɚɞɢɹɯ ɤɥɟɬɨɱɧɨɝɨ ɰɢɤɥɚ. 2.2. Ɇɨɧɨɧɭɤɥɟɚɪɧɵɟ ɤɥɟɬɤɢ Ɇɨɧɨɧɭɤɥɟɚɪɧɵɟ ɤɥɟɬɤɢ ɜɵɞɟɥɹɥɢ ɦɟɬɨɞɚɦɢ ɝɪɚɞɢɟɧɬɧɨɝɨ ɰɟɧɬɪɢɮɭɝɢɪɨɜɚɧɢɹ ɫ ɢɫɩɨɥɶɡɨɜɚɧɢɟɦ Ficoll-Paque ɩɥɨɬɧɨɫɬɶɸ d=1,077 ɝ/ɫɦ3, ɨɛɪɚɛɨɬɤɢ ɨɛɪɚɡɰɨɜ ɥɢɡɢɪɭɸɳɢɦ ɪɚɫɬɜɨɪɨɦ, ɫɨɫɬɨɹɳɟɝɨ ɢɡ ɯɥɨɪɢɞɚ ɚɦɦɨɧɢɹ, ɝɢɞɪɨɤɚɪɛɨɧɚɬɚ ɤɚɥɢɹ ɢ ɧɚɬɪɢɟɜɨɣ ɫɨɥɢ ɷɬɢɥɟɧɞɢɚɦɢɧɭɤɫɭɫɧɨɣ ɤɢɫɥɨɬɵ ɜ ɫɨɨɬɧɨɲɟɧɢɢ 1:9 ɢ ɫɟɞɢɦɟɧɬɚɰɢɢ ɤɥɟɬɨɤ ɜ 3% ɪɚɫɬɜɨɪɟ ɠɟɥɚɬɢɧɚ ɩɭɬɟɦ ɧɚɫɥɚɢɜɚɧɢɹ ɝɟɩɚɪɢɧɢɡɢɪɨɜɚɧɧɵɯ ɨɛɪɚɡɰɨɜ ɜ ɫɨɨɬɧɨɲɟɧɢɢ 1:3. 2.3. Ƚɟɦɨɩɨɷɬɢɱɟɫɤɢɟ ɫɬɜɨɥɨɜɵɟ ɤɥɟɬɤɢ (ȽɋɄ) ɂɫɩɨɥɶɡɨɜɚɧɧɵɟ ɜ ɨɩɵɬɚɯ ȽɋɄ ɛɵɥɢ ɥɸɛɟɡɧɨ ɩɪɟɞɨɫɬɚɜɥɟɧɵ ɛɚɧɤɨɦ ɫɬɜɨɥɨɜɵɯ ɤɥɟɬɨɤ (London Cord Blood Bank, Deansbrook Road, Edgeware HA8 9BD). Ɋɚɡɦɧɨɠɟɧɢɟ ȽɋɄ ɨɫɭɳɟɫɬɜɥɹɥɢ in vitro. Ⱦɥɹ ɜɵɞɟɥɟɧɢɹ ɢ ɨɱɢɫɬɤɢ ȽɋɄ (ɪɢɫ. 2.1) ɩɪɢɦɟɧɹɥɢ ɩɪɨɰɟɞɭɪɭ ɪɚɡɞɟɥɟɧɢɹ ɫɭɫɩɟɧɡɢɢ ɤɥɟɬɨɤ ɜ ɝɪɚɞɢɟɧɬɚɯ ɮɢɤɨɥɥɚ (Ficoll-Paque, Pharmacia). ɉɟɪɜɵɦ ɲɚɝɨɦ ɜɵɞɟɥɟɧɢɹ ȽɋɄ ɹɜɥɹɟɬɫɹ ɜɧɟɫɟɧɢɟ 20 ɦɥ 35 ɤɥɟɬɨɱɧɨɣ ɫɭɫɩɟɧɡɢɢ ɜ ɪɨɫɬɨɜɭɸ ɫɪɟɞɭ IMDM ɢ 2% ɎȻɋ ɜ 50 ɦɥ ɰɟɧɬɪɢɮɭɠɧɭɸ ɩɪɨɛɢɪɤɭ. Ɂɚɬɟɦ 10 ɦɥ Ficoll-Paque (FP) ɧɚɫɥɚɢɜɚɥɢɫɶ ɩɨɞ ɨɛɪɚɡɟɰ ɤɥɟɬɨɤ. Ɋɚɡɞɟɥɟɧɢɟ ɨɛɪɚɡɰɚ ɞɨɫɬɢɝɚɥɨɫɶ ɰɟɧɬɪɢɮɭɝɢɪɨɜɚɧɢɟɦ (400g) ɜ ɬɟɱɟɧɢɟ 35 ɦɢɧ ɩɪɢ 20°C. Ɉɬɬɚɢɜɚɧɢɟ ɉɨɞɫɱɟɬ ɤɥɟɬɨɤ Ɋɚɡɞɟɥɟɧɢɟ ɜ Ficoll-Paque Ʉɭɥɶɬɢɜɢɪɨɜɚɧɢɟ ɉɨɞɫɱɟɬ ɤɥɟɬɨɤ ȼɵɞɟɥɟɧɢɟ CD34+ ɫ ɩɨɦɨɳɶɸ ɦɚɝɧɢɬɧɵɯ ɫɮɟɪ ɉɨɞɫɱɟɬ ɤɥɟɬɨɤ ɉɪɨɬɨɱɧɚɹ ɰɢɬɨɦɟɬɪɢɹ ɐɢɬɨɫɩɢɧ Ɉɤɪɚɲɢɜɚɧɢɟ ɩɨ Wright Ʉɭɥɶɬɢɜɢɪɨɜɚɧɢɟ ɉɪɨɬɟɨɦɧɵɣ ɚɧɚɥɢɡ (∼2×106 ɤɥɟɬɨɤ) Ʉɭɥɶɬɢɜɢɪɨɜɚɧɢɟ ɂɦɦɭɧɨɝɢɫɬɨɥɨɝɢɱɟɫɤɨɟ ɨɤɪɚɲɢɜɚɧɢɟ Ɋɢɫ. 2.1. Ɍɢɩɢɱɧɚɹ ɛɥɨɤ-ɫɯɟɦɚ ɨɱɢɫɬɤɢ, ɤɭɥɶɬɢɜɢɪɨɜɚɧɢɹ ɢ ɜɵɞɟɥɟɧɢɹ ȽɋɄ 36 ɉɪɢ ɢɫɩɨɥɶɡɨɜɚɧɢɢ ɫɬɟɪɢɥɶɧɨɣ ɩɥɚɫɬɢɤɨɜɨɣ ɩɢɩɟɬɤɢ ɫɟɪɟɞɢɧɧɵɣ ɫɥɨɣ (ɥɢɦɮɨɰɢɬɵ) ɩɟɪɟɧɨɫɢɥɫɹ ɜ ɱɢɫɬɭɸ ɰɟɧɬɪɢɮɭɠɧɭɸ ɩɪɨɛɢɪɤɭ. ɇɚ ɫɥɟɞɭɸɳɟɦ ɷɬɚɩɟ ɤ ɥɢɦɮɨɰɢɬɚɦ ɜ ɩɪɨɛɢɪɤɟ ɞɨɛɚɜɥɹɥɨɫɶ 10 ɦɥ PBS. Ʉɥɟɬɤɢ ɫɭɫɩɟɧɞɢɪɨɜɚɥɢ ɚɤɤɭɪɚɬɧɵɦ ɜɫɚɫɵɜɚɧɢɟɦ ɢ ɜɵɩɭɫɤɚɧɢɟɦ ɢɡ ɩɢɩɟɬɤɢ, ɡɚɬɟɦ ɰɟɧɬɪɢɮɭɝɢɪɨɜɚɥɢ (200g) ɜ ɬɟɱɟɧɢɟ 10 ɦɢɧ ɩɪɢ 20°C. ɋɭɩɟɪɧɚɬɚɧɬ ɫɥɢɜɚɥɢ ɢ ɫɭɫɩɟɧɞɢɪɨɜɚɥɢ ɥɢɦɮɨɰɢɬɵ ɜ 10 ɦɥ PBS ɜɫɚɫɵɜɚɧɢɟɦ ɢ ɜɵɩɭɫɤɚɧɢɟɦ ɢɡ ɩɢɩɟɬɤɢ. Ɂɚɬɟɦ ɨɛɪɚɡɟɰ ɰɟɧɬɪɢɮɭɝɢɪɨɜɚɥɢ (200g) ɜ ɬɟɱɟɧɢɟ 10 ɦɢɧ ɩɪɢ 20°C ɢ ɩɨɞɜɟɪɝɚɥɢ ɨɱɢɫɬɤɟ. 2.4. ȼɵɞɟɥɟɧɢɟ CD34+ ɫ ɩɨɦɨɳɶɸ ɦɚɝɧɢɬɧɵɯ ɫɮɟɪ ɉɪɨɰɟɞɭɪɚ ɜɤɥɸɱɚɟɬ ɜ ɫɟɛɹ ɪɟɫɭɫɩɟɧɞɢɪɨɜɚɧɢɟ ɤɥɟɬɨɱɧɨɝɨ ɫɝɭɫɬɤɚ ɜ 300 ɦɤɥ ɛɭɮɟɪɚ (ɧɚ 108 ɤɥɟɬɨɤ). ɋɥɟɞɭɸɳɚɹ ɫɬɚɞɢɹ – ɞɨɛɚɜɥɟɧɢɟ 100 ɦɤɥ FcR ɛɥɨɤɢɪɭɸɳɟɝɨ ɪɟɚɝɟɧɬɚ ɧɚ 108 ɤɥɟɬɨɤ, ɩɟɪɟɦɟɲɢɜɚɧɢɟ ɢ ɞɨɛɚɜɥɟɧɢɟ 100 ɦɤɥ ɝɚɩɬɟɧ-ɚɧɬɢɬɟɥ ɧɚ 108 ɤɥɟɬɨɤ, ɫɦɟɲɢɜɚɧɢɟ ɢ ɢɧɤɭɛɢɪɨɜɚɧɢɟ ɜ ɬɟɱɟɧɢɟ 15 ɦɢɧ ɩɪɢ 4°C ɞɥɹ ɞɨɫɬɢɠɟɧɢɹ ɨɩɬɢɦɚɥɶɧɨɝɨ ɫɥɢɩɚɧɢɹ. Ʉɨɧɟɱɧɵɣ ɨɛɴɟɦ ɞɥɹ ɦɟɬɤɢ ɫɨɫɬɚɜɥɹɟɬ 500 ɦɤɥ ɧɚ 108 ɤɥɟɬɨɤ. Ɂɚɬɟɦ ɤɥɟɬɤɢ ɬɳɚɬɟɥɶɧɨ ɩɪɨɦɵɜɚɸɬ ɛɭɮɟɪɨɦ, ɞɨɛɚɜɥɹɹ 10–20 ɪɚɡ ɨɤɪɚɲɢɜɚɸɳɢɣ ɨɛɴɟɦ (5–10 ɦɥ ɧɚ 108 ɤɥɟɬɨɤ), ɰɟɧɬɪɢɮɭɝɢɪɭɸɬ ɢ ɩɨɥɧɨɫɬɶɸ ɫɥɢɜɚɸɬ ɫɭɩɟɪɧɚɬɚɧɬ, ɡɚɬɟɦ ɪɟɫɭɫɩɟɧɞɢɪɭɸɬ ɫɝɭɫɬɨɤ ɨɫɬɨɪɨɠɧɨ, ɞɨɛɚɜɥɹɹ ɛɭɮɟɪ ɞɨ ɤɨɧɟɱɧɨɝɨ ɨɛɴɟɦɚ 400 ɦɤɥ ɧɚ 108 ɤɥɟɬɨɤ. Ɂɚɬɟɦ ɞɨɛɚɜɥɹɸɬ 100 ɦɤɥ ɚɧɬɢɝɚɩɬɟɧɨɜɵɯ ɦɢɤɪɨɫɮɟɪ ɧɚ 108 ɤɥɟɬɨɤ (ɤɨɧɟɱɧɵɣ ɦɟɬɹɳɢɣ ɨɛɴɟɦ ɫɨɫɬɚɜɥɹɟɬ 500 ɦɤɥ ɧɚ 108 ɤɥɟɬɨɤ), ɬɳɚɬɟɥɶɧɨ ɩɟɪɟɦɟɲɢɜɚɸɬ ɢ ɢɧɤɭɛɢɪɭɸɬ 15 ɦɢɧ ɩɪɢ ɬɟɦɩɟɪɚɬɭɪɟ 4°C. Ʉɥɟɬɤɢ ɡɚɬɟɦ ɨɬɦɵɜɚɸɬ ɢ ɪɟɫɭɫɩɟɧɞɢɪɭɸɬ, ɫ ɤɥɟɬɨɱɧɵɦ ɫɝɭɫɬɤɨɦ, ɢɧɤɭɛɢɪɭɟɦɵɦ ɜ 500 ɦɤɥ ɛɭɮɟɪɚ ɧɚ 108 ɤɥɟɬɨɤ. Ʉɨɥɨɧɤɚ ɞɥɹ ɦɚɝɧɢɬɧɨɣ ɫɟɩɚɪɚɰɢɢ ɨɩɪɟɞɟɥɹɟɬɫɹ ɭɫɥɨɜɢɹɦɢ ɷɤɫɩɟɪɢɦɟɧɬɚ. Ⱦɥɹ ɦɚɫɫ-ɫɩɟɤɬɪɨɦɟɬɪɢɢ ɤɨɥɨɧɤɚ ɡɚɩɨɥɧɹɟɬɫɹ ɢ ɩɪɨɦɵɜɚɟɬɫɹ 500 ɦɤɥ ɛɭɮɟɪɚ, ɤɥɟɬɤɢ ɩɪɨɩɭɫɤɚɸɬɫɹ ɱɟɪɟɡ ɮɢɥɶɬɪ (ɫ ɦɟɲ 30 ɦɤɥ, ɧɟɣɥɨɧ), ɫ ɭɞɚɥɟɧɢɟɦ ɫɝɭɫɬɤɨɜ, ɮɢɥɶɬɪ ɫɦɚɱɢɜɚ- 37 ɟɬɫɹ ɛɭɮɟɪɨɦ ɩɟɪɟɞ ɢɫɩɨɥɶɡɨɜɚɧɢɟɦ. Ɂɚɬɟɦ ɤɥɟɬɤɢ ɧɚɧɨɫɹɬɫɹ ɧɚ ɤɨɥɨɧɤɭ, ɩɪɨɩɭɫɤɚɸɬɫɹ ɱɟɪɟɡ ɧɟɟ ɞɥɹ ɪɚɡɞɟɥɟɧɢɹ ɢ ɩɪɨɦɵɜɚɸɬɫɹ ɛɭɮɟɪɨɦ 3×500 ɦɤɥ, ɤɨɥɨɧɤɚ ɫɧɢɦɚɟɬɫɹ ɫ ɫɟɩɚɪɚɬɨɪɚ, ɩɨɦɟɳɚɟɬɫɹ ɜ ɩɨɞɯɨɞɹɳɭɸ ɩɪɨɛɢɪɤɭ, ɧɚ ɤɨɥɨɧɤɭ ɧɚɧɨɫɢɬɫɹ 1 ɦɥ ɛɭɮɟɪɚ ɢ ɷɥɸɢɪɭɸɬɫɹ ɡɚɞɟɪɠɚɧɧɵɟ ɤɥɟɬɤɢ ɩɪɢ ɢɫɩɨɥɶɡɨɜɚɧɢɢ ɩɥɭɧɠɟɪɚ, ɱɬɨ ɦɢɧɢɦɢɡɢɪɭɟɬ ɤɨɥɢɱɟɫɬɜɨ ɤɥɟɬɨɤ, ɩɨɬɟɪɹɧɧɵɯ ɧɚ ɮɢɥɶɬɪɟ. ɗɬɚ ɫɬɚɞɢɹ ɩɨɜɬɨɪɹɟɬɫɹ ɧɚɧɟɫɟɧɢɟɦ ɷɥɸɢɪɨɜɚɧɧɵɯ ɤɥɟɬɨɤ ɧɚ ɧɨɜɭɸ ɤɨɥɨɧɤɭ ɞɥɹ ɦɟɧɟɟ ɱɟɦ 107 CD34+ ɤɥɟɬɨɤ, ɡɚɬɟɦ ɫɦɵɜɚɸɬɫɹ ɢ ɷɥɸɢɪɭɸɬɫɹ ɛɭɮɟɪɨɦ ɡɚɞɟɪɠɚɧɧɵɟ ɤɥɟɬɤɢ. Ⱦɥɹ ɤɭɥɶɬɢɜɢɪɨɜɚɧɢɹ ɜɵɞɟɥɟɧɧɵɯ ȽɋɄ ɢɫɩɨɥɶɡɨɜɚɥɢ ɩɢɬɚɬɟɥɶɧɵɟ ɫɪɟɞɵ RPMI 1640 (Sigma), L-15 (Sigma), DɆȿɆ/F12 (Sigma) ɢ ɉɋɉ, ɫɨɞɟɪɠɚɳɢɟ 10% ɮɟɬɚɥɶɧɨɣ ɫɵɜɨɪɨɬɤɢ ɩɥɨɞɚ ɤɨɪɨɜɵ. Ʉɥɟɬɤɢ ɜɵɫɟɜɚɥɢ ɜ ɤɭɥɶɬɭɪɚɥɶɧɵɟ 24 ɥɭɧɨɱɧɵɟ ɩɥɚɲɤɢ. Ʉɭɥɶɬɢɜɢɪɨɜɚɧɢɟ ɩɪɨɜɨɞɢɥɢ ɩɪɢ 37°ɋ ɜ ɭɜɥɚɠɧɟɧɧɨɣ ɚɬɦɨɫɮɟɪɟ ɫɨɞɟɪɠɚɳɟɣ 5%ɋɈ2. Ⱦɜɭɯɧɟɞɟɥɶɧɚɹ ɩɪɨɰɟɞɭɪɚ ɤɭɥɶɬɢɜɢɪɨɜɚɧɢɹ ɋɄ ɢɡ ɩɭɩɨɜɢɧɧɨɣ ɤɪɨɜɢ ɞɚɧɚ ɜ ɬɚɛɥ. 2.1. Ɍɚɛɥɢɰɚ 2.1. ɋɯɟɦɚ ɷɤɫɩɟɪɢɦɟɧɬɚ ɞɥɹ ɢɫɫɥɟɞɨɜɚɧɢɹ ȽɋɄ ɩɪɢ ɞɜɭɯɧɟɞɟɥɶɧɨɦ ɤɭɥɶɬɢɜɢɪɨɜɚɧɢɢ Ⱦɧɢ Ɋɚɡɞɟɥɟɧɢɟ ɜ ȼɵɞɟɥɟɧɢɟ CD34+ Ʉɭɥɶɬɢɜɢ- ɉɪɨɬɨɱɧɚɹ ɉɨɞɫɱɟɬ ɐɢɬɨ- ɉɪɨɬɟɨɦFicoll-Paque ɫ ɩɨɦɨɳɶɸ ɦɚɝ- ɪɨɜɚɧɢɟ ɰɢɬɨɦɟɬɪɢɹ ɤɥɟɬɨɤ ɫɩɢɧ ɧɵɣ ɚɧɚɥɢɡ ɧɢɬɧɵɯ ɫɮɟɪ 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 ɉɨɫɟɜ Ȼɚɡɨɜɵɣ ɭɪɨɜɟɧɶ Ɂɚɦɟɧɚ ɫɪɟɞɵ Ɂɚɦɟɧɚ ɫɪɟɞɵ Ɂɚɦɟɧɚ ɫɪɟɞɵ Ɂɚɦɟɧɚ ɫɪɟɞɵ 38 2.5. Ʉɥɟɬɤɢ ɢɡ ɢɧɬɢɦɵ (ɦɟɞɢɢ) ɚɨɪɬɵ Ɇɚɬɟɪɢɚɥ ɞɥɹ ɢɫɫɥɟɞɨɜɚɧɢɹ ɩɨɥɭɱɚɥɢ ɢɡ ɚɭɬɨɩɫɢɣɧɵɯ ɨɛɪɚɡɰɨɜ ɝɪɭɞɧɨɝɨ ɨɬɞɟɥɚ ɚɨɪɬ ɦɭɠɱɢɧ ɢ ɠɟɧɳɢɧ ɜ ɜɨɡɪɚɫɬɟ 40–65 ɥɟɬ ɜ ɬɟɱɟɧɢɟ 1,5–3 ɱɚɫɨɜ ɩɨɫɥɟ ɜɧɟɡɚɩɧɨɣ ɫɦɟɪɬɢ. ɉɪɢɱɢɧɨɣ ɫɦɟɪɬɢ ɜ ɩɨɞɚɜɥɹɸɳɟɦ ɛɨɥɶɲɢɧɫɬɜɟ ɫɥɭɱɚɟɜ ɛɵɥɚ ɨɫɬɪɚɹ ɫɟɪɞɟɱɧɨɫɨɫɭɞɢɫɬɚɹ ɧɟɞɨɫɬɚɬɨɱɧɨɫɬɶ. Ɉɛɪɚɛɨɬɤɭ ɚɭɬɨɩɫɢɣɧɨɝɨ ɦɚɬɟɪɢɚɥɚ ɩɪɨɜɨɞɢɥɢ ɜ ɫɬɟɪɢɥɶɧɵɯ ɭɫɥɨɜɢɹɯ. ɉɨɫɥɟ ɦɟɯɚɧɢɱɟɫɤɨɝɨ ɭɞɚɥɟɧɢɹ ɚɞɜɟɧɬɢɰɢɢ ɚɨɪɬɭ ɪɚɫɫɟɤɚɥɢ ɜɞɨɥɶ ɢ ɩɪɨɦɵɜɚɥɢ ɜ ɯɨɥɨɞɧɨɦ ɮɨɫɮɚɬɧɨɦ ɛɭɮɟɪɟ ɞɥɹ ɭɞɚɥɟɧɢɹ ɥɸɛɵɯ ɫɥɟɞɨɜ ɤɪɨɜɢ. ɂɡ ɥɨɫɤɭɬɚ ɚɨɪɬɵ ɜɵɪɟɡɚɥɢ ɭɱɚɫɬɤɢ, ɧɟ ɩɨɪɚɠɟɧɧɵɟ ɚɬɟɪɨɫɤɥɟɪɨɡɨɦ, ɚ ɬɚɤɠɟ ɭɱɚɫɬɤɢ, ɫɨɨɬɜɟɬɫɬɜɭɸɳɢɟ ɪɚɡɥɢɱɧɵɦ ɜɢɞɚɦ ɚɬɟɪɨɫɤɥɟɪɨɬɢɱɟɫɤɢɯ ɩɨɪɚɠɟɧɢɣ (ɠɢɪɨɜɚɹ ɢɧɮɢɥɶɬɪɚɰɢɹ, ɠɢɪɨɜɚɹ ɩɨɥɨɫɚ, ɥɢɩɨɮɢɛɪɨɡɧɚɹ ɛɥɹɲɤɚ, ɮɢɛɪɨɡɧɚɹ ɛɥɹɲɤɚ), ɜ ɫɨɨɬɜɟɬɫɬɜɢɢ ɫ ɤɥɚɫɫɢɮɢɤɚɰɢɟɣ Stary [80]. ɉɪɢ ɢɞɟɧɬɢɮɢɤɚɰɢɢ ɬɢɩɚ ɩɨɪɚɠɟɧɢɹ ɪɭɤɨɜɨɞɫɬɜɨɜɚɥɢɫɶ ɫɥɟɞɭɸɳɢɦɢ ɩɪɟɞɫɬɚɜɥɟɧɢɹɦɢ. ȼɧɟɲɧɟ ɧɟɩɨɪɚɠɟɧɧɵɟ ɭɱɚɫɬɤɢ ɚɨɪɬ ɢ ɭɱɚɫɬɤɢ ɫ ɚɬɟɪɨɫɤɥɟɪɨɬɢɱɟɫɤɢɦɢ ɩɨɪɚɠɟɧɢɹɦɢ ɢɞɟɧɬɢɮɢɰɢɪɨɜɚɥɢ ɦɚɤɪɨɫɤɨɩɢɱɟɫɤɢ, ɚ ɡɚɬɟɦ ɦɢɤɪɨɫɤɨɩɢɱɟɫɤɢ ɜ ɫɨɨɬɜɟɬɫɬɜɢɢ ɫ ɤɥɚɫɫɢɮɢɤɚɰɢɟɣ ɋɨɜɟɬɚ ɩɨ ɚɬɟɪɨɫɤɥɟɪɨɡɭ Ⱥɦɟɪɢɤɚɧɫɤɨɝɨ Ɉɛɳɟɫɬɜɚ ɩɨ ɢɡɭɱɟɧɢɸ ɫɟɪɞɰɚ. ɍɱɚɫɬɤɢ ɢɧɬɢɦɵ ɫ ɧɚɱɚɥɶɧɵɦɢ ɩɨɪɚɠɟɧɢɹɦɢ (I ɬɢɩ ɩɨɪɚɠɟɧɢɹ) ɦɚɤɪɨɫɤɨɩɢɱɟɫɤɢ ɩɪɟɞɫɬɚɜɥɹɥɢ ɫɨɛɨɣ ɭɱɚɫɬɤɢ ɫ ɝɥɚɞɤɨɣ ɠɟɥɬɨɜɚɬɨɣ ɩɨɜɟɪɯɧɨɫɬɶɸ, ɢɧɨɝɞɚ ɫ ɦɟɥɤɢɦɢ ɠɟɥɬɵɦɢ ɬɨɱɤɚɦɢ. Ɇɢɤɪɨɫɤɨɩɢɱɟɫɤɢɟ ɢɡɦɟɧɟɧɢɹ ɛɵɥɢ ɦɢɧɢɦɚɥɶɧɵ. ɇɚɛɥɸɞɚɥɢɫɶ ɧɟɛɨɥɶɲɢɟ ɧɚɤɨɩɥɟɧɢɹ ɜɧɟɤɥɟɬɨɱɧɵɯ ɥɢɩɢɞɧɵɯ ɤɚɩɟɥɶ ɜ ɫɨɟɞɢɧɢɬɟɥɶɧɨ-ɬɤɚɧɧɨɦ ɦɚɬɪɢɤɫɟ. ɉɨɦɢɦɨ ɨɫɟɞɥɵɯ ɤɥɟɬɨɤ ɜ ɭɱɚɫɬɤɚɯ ɧɚɱɚɥɶɧɵɯ ɩɨɪɚɠɟɧɢɣ ɦɨɠɧɨ ɛɵɥɨ ɨɛɧɚɪɭɠɢɬɶ ɭɜɟɥɢɱɟɧɧɨɟ ɩɨ ɫɪɚɜɧɟɧɢɸ ɫ ɜɧɟɲɧɟ ɧɟɢɡ- 39 ɦɟɧɟɧɧɨɣ ɢɧɬɢɦɨɣ ɤɨɥɢɱɟɫɬɜɨ ɦɨɧɨɧɭɤɥɟɚɪɧɵɯ ɤɥɟɬɨɤ. ɇɢɤɚɤɢɯ ɧɚɪɭɲɟɧɢɣ ɜ ɫɬɪɭɤɬɭɪɟ ɬɤɚɧɢ ɧɟ ɜɵɹɜɥɹɥɨɫɶ. ɀɢɪɨɜɵɟ ɩɨɥɨɫɵ (ɩɨɪɚɠɟɧɢɹ II ɬɢɩɚ) ɦɚɤɪɨɫɤɨɩɢɱɟɫɤɢ ɩɪɟɞɫɬɚɜɥɹɥɢ ɫɨɛɨɣ ɩɨɥɨɫɤɢ ɢ ɬɨɱɤɢ ɠɟɥɬɨɝɨ ɰɜɟɬɚ, ɧɟɦɧɨɝɨ ɜɵɫɬɭɩɚɸɳɢɟ ɧɚɞ ɩɨɜɟɪɯɧɨɫɬɶɸ ɫɨɫɭɞɚ. ɑɚɫɬɨ ɦɨɠɧɨ ɛɵɥɨ ɨɛɧɚɪɭɠɢɬɶ ɠɢɪɨɜɵɟ ɩɨɥɨɫɤɢ, ɫɥɢɜɲɢɟɫɹ ɦɟɠɞɭ ɫɨɛɨɣ ɜ ɛɨɥɟɟ ɤɪɭɩɧɵɟ ɫɬɪɭɤɬɭɪɵ (ɤɥɚɫɬɟɪɵ). ɇɚ ɫɪɟɡɚɯ ɬɤɚɧɢ ɥɢɩɢɞɵ ɜɵɹɜɥɹɥɢɫɶ ɜ ɨɫɧɨɜɧɨɦ ɜɧɭɬɪɢɤɥɟɬɨɱɧɨ. ȼ ɫɨɟɞɢɧɢɬɟɥɶɧɨ-ɬɤɚɧɧɨɦ ɦɚɬɪɢɤɫɟ ɨɛɧɚɪɭɠɢɜɚɥɢɫɶ ɬɚɤɠɟ ɜɧɟɤɥɟɬɨɱɧɵɟ ɥɢɩɢɞɵ. ɂɧɨɝɞɚ ɜ ɠɢɪɨɜɵɯ ɩɨɥɨɫɚɯ ɧɚɛɥɸɞɚɥɨɫɶ ɨɛɢɥɶɧɨɟ ɪɚɡɪɚɫɬɚɧɢɟ ɜɧɟɤɥɟɬɨɱɧɨɝɨ ɦɚɬɪɢɤɫɚ. Ʌɢɩɨɮɢɛɪɨɡɧɵɟ ɛɥɹɲɤɢ (ɩɨɪɚɠɟɧɢɹ Va ɬɢɩɚ). ɉɪɢ ɦɚɤɪɨɫɤɨɩɢɱɟɫɤɨɦ ɢɡɭɱɟɧɢɢ ɥɢɩɨɮɢɛɪɨɡɧɵɟ ɛɥɹɲɤɢ ɜɵɝɥɹɞɟɥɢ ɤɚɤ ɫɢɥɶɧɨ ɜɵɫɬɭɩɚɸɳɢɟ ɧɚɞ ɥɸɦɢɧɚɥɶɧɨɣ ɩɨɜɟɪɯɧɨɫɬɶɸ ɠɟɥɬɨɜɚɬɵɟ ɢɥɢ ɩɟɪɥɚɦɭɬɪɨɜɵɟ, ɤɪɭɝɥɵɟ ɢɥɢ ɷɥɥɢɩɫɨɢɞɧɵɟ ɨɛɪɚɡɨɜɚɧɢɹ. Ɇɢɤɪɨɫɤɨɩɢɱɟɫɤɢ ɜ ɷɬɢɯ ɩɨɪɚɠɟɧɢɹɯ ɨɛɧɚɪɭɠɢɜɚɥɢɫɶ ɜɫɟ ɢɡɦɟɧɟɧɢɹ, ɯɚɪɚɤɬɟɪɧɵɟ ɞɥɹ ɠɢɪɨɜɵɯ ɩɨɥɨɫ: ɧɚɤɨɩɥɟɧɢɟ ɜɧɭɬɪɢɤɥɟɬɨɱɧɵɯ ɥɢɩɢɞɨɜ, ɪɚɡɪɚɫɬɚɧɢɟ ɜɧɟɤɥɟɬɨɱɧɨɝɨ ɦɚɬɪɢɤɫɚ. Ʉɪɨɦɟ ɷɬɨɝɨ, ɜ ɥɢɩɨɮɢɛɪɨɡɧɵɯ ɛɥɹɲɤɚɯ ɜɵɹɜɥɹɥɨɫɶ ɦɚɫɫɢɜɧɨɟ ɧɟɤɪɨɬɢɱɟɫɤɨɟ ɹɞɪɨ ɢ ɪɚɫɩɨɥɨɠɟɧɧɚɹ ɧɚɞ ɧɢɦ ɫɨɟɞɢɧɢɬɟɥɶɧɨ-ɬɤɚɧɧɚɹ ɩɨɤɪɵɲɤɚ. ȼ ɥɢɩɨɮɢɛɪɨɡɧɵɯ ɛɥɹɲɤɚɯ ɢɦɟɥɢɫɶ ɭɱɚɫɬɤɢ, ɩɨ ɦɨɪɮɨɥɨɝɢɢ ɩɨɯɨɠɢɟ ɧɚ ɭɱɚɫɬɤɢ ɠɢɪɨɜɵɯ ɩɨɪɚɠɟɧɢɣ – ɩɥɟɱɢ ɥɢɩɨɮɢɛɪɨɡɧɵɯ ɛɥɹɲɟɤ. Ɏɢɛɪɨɡɧɵɟ ɛɥɹɲɤɢ (ɩɨɪɚɠɟɧɢɹ Vc ɬɢɩɚ). Ɏɢɛɪɨɡɧɵɟ ɛɥɹɲɤɢ ɦɚɤɪɨɫɤɨɩɢɱɟɫɤɢ ɩɪɟɞɫɬɚɜɥɹɥɢ ɫɨɛɨɣ ɫɢɥɶɧɨ ɩɪɢɩɨɞɧɹɬɵɟ ɠɟɦɱɭɠɧɨɝɨ ɰɜɟɬɚ ɨɤɪɭɝɥɵɟ ɢɥɢ ɨɜɚɥɶɧɵɟ ɨɛɪɚɡɨɜɚɧɢɹ, ɦɢɤɪɨɫɤɨɩɢɱɟɫɤɢ ɫɨɫɬɨɹɳɢɟ ɜ ɨɫɧɨɜɧɨɦ ɢɡ ɝɪɭɛɨɝɨ ɫɨɟɞɢɧɢɬɟɥɶɧɨ-ɬɤɚɧɧɨɝɨ ɦɚɬɪɢɤɫɚ, ɫ «ɡɚɦɭɪɨɜɚɧɧɵɦɢ» ɜ ɧɟɦ ɤɥɟɬɤɚɦɢ. Ʌɢɩɢɞɧɵɣ ɤɨɦɩɨɧɟɧɬ ɛɵɥ ɦɢɧɢɦɚɥɶɧɵɦ ɢɥɢ ɨɬɫɭɬɫɬɜɨɜɚɥ. 40 Ɂɚɬɟɦ ɫ ɩɨɦɨɳɶɸ ɩɢɧɰɟɬɨɜ ɢɧɬɢɦɭ ɨɬɞɟɥɹɥɢ ɨɬ ɦɟɞɢɢ, ɩɪɢ ɷɬɨɦ ɪɚɡɞɟɥɟɧɢɟ ɫɥɨɟɜ ɩɪɨɢɫɯɨɞɢɥɨ ɩɨ ɜɧɭɬɪɟɧɧɟɣ ɩɨɝɪɚɧɢɱɧɨɣ ɷɥɚɫɬɢɱɟɫɤɨɣ ɦɟɦɛɪɚɧɟ. ȼɵɞɟɥɟɧɧɵɟ ɨɛɪɚɡɰɵ ɪɚɡɦɟɪɨɦ 1×1 ɫɦ ɜɧɨɜɶ ɬɳɚɬɟɥɶɧɨ ɩɪɨɦɵɜɚɥɢ ɜ ɯɨɥɨɞɧɨɦ ɮɨɫɮɚɬɧɨɦ ɛɭɮɟɪɟ, ɧɟɦɟɞɥɟɧɧɨ ɡɚɦɨɪɚɠɢɜɚɥɢ ɜ ɠɢɞɤɨɦ ɚɡɨɬɟ ɢ ɪɚɫɬɢɪɚɥɢ ɮɚɪɮɨɪɨɜɵɦ ɩɟɫɬɢɤɨɦ ɜ ɮɚɪɮɨɪɨɜɨɣ ɫɬɭɩɤɟ ɞɨ ɩɨɪɨɲɤɨɨɛɪɚɡɧɨɝɨ ɫɨɫɬɨɹɧɢɹ. ɉɨɫɥɟ ɭɩɚɪɢɜɚɧɢɹ ɠɢɞɤɨɝɨ ɚɡɨɬɚ ɩɪɢ ɤɨɦɧɚɬɧɨɣ ɬɟɦɩɟɪɚɬɭɪɟ ɨɛɪɚɡɰɵ ɥɢɨɮɢɥɢɡɢɪɨɜɚɥɢ ɜ ɥɢɨɮɢɥɶɧɨɣ ɫɭɲɤɟ ɜ ɬɟɱɟɧɢɟ 6 ɱɚɫɨɜ. ɏɪɚɧɟɧɢɟ ɨɛɪɚɡɰɨɜ ɜɩɥɨɬɶ ɞɨ ɜɵɞɟɥɟɧɢɹ ɛɟɥɤɨɜ ɩɪɨɜɨɞɢɥɢ ɩɪɢ –80°ɋ ɜ ɧɢɡɤɨɬɟɦɩɟɪɚɬɭɪɧɨɦ ɦɨɪɨɡɢɥɶɧɢɤɟ. Ɂɚɦɨɪɨɠɟɧɧɵɟ ɨɛɪɚɡɰɵ ɩɨɞɜɟɪɝɚɥɢ ɢɡɦɟɥɶɱɟɧɢɸ ɜ ɚɬɦɨɫɮɟɪɟ ɠɢɞɤɨɝɨ ɚɡɨɬɚ, ɢɡɛɟɝɚɹ ɨɬɬɚɢɜɚɧɢɹ. ɉɨɥɭɱɟɧɧɵɣ ɩɨɪɨɲɨɤ ɪɚɫɬɜɨɪɹɥɢ (ɫɭɫɩɟɧɞɢɪɨɜɚɥɢ) ɜ ɛɭɮɟɪɧɨɦ ɪɚɫɬɜɨɪɟ ɦɨɱɟɜɢɧɵ ɜ ɫɨɨɬɧɨɲɟɧɢɢ 1 ɝ ɩɨɪɨɲɤɚ ɧɚ 7 ɦɥ ɛɭɮɟɪɚ ɩɪɢ ɩɨɫɬɨɹɧɧɨɦ ɜɫɬɪɹɯɢɜɚɧɢɢ ɩɪɢ ɤɨɦɧɚɬɧɨɣ ɬɟɦɩɟɪɚɬɭɪɟ. ɋɭɫɩɟɧɡɢɸ ɰɟɧɬɪɢɮɭɝɢɪɨɜɚɥɢ ɩɪɢ 15000 g ɜ ɬɟɱɟɧɢɟ 30 ɦɢɧ ɩɪɢ ɤɨɦɧɚɬɧɨɣ ɬɟɦɩɟɪɚɬɭɪɟ. Ɋɚɡɞɟɥɟɧɧɵɟ ɮɪɚɤɰɢɢ ɯɪɚɧɢɥɢ ɩɪɢ – 80°C. ɉɟɪɟɞ ɩɪɨɜɟɞɟɧɢɟɦ ɷɥɟɤɬɪɨɮɨɪɟɡɚ ɞɨɛɚɜɥɹɥɢ ɢɧɝɢɛɢɬɨɪ ɩɪɨɬɟɚɡ. Ⱦɥɹ ɜɵɞɟɥɟɧɢɹ ɛɟɥɤɨɜ ɢɡ ɩɨɪɨɲɤɨɨɛɪɚɡɧɵɯ ɨɛɪɚɡɰɨɜ ɢɫɩɨɥɶɡɨɜɚɥɢ ɞɜɚ ɦɟɬɨɞɚ. ȼ ɩɟɪɜɨɦ ɦɟɬɨɞɟ ɩɨɪɨɲɨɤ ɪɚɫɬɜɨɪɹɥɢ ɜ ɦɨɱɟɜɢɧɧɨɦ ɛɭɮɟɪɟ pH=8,0 (ɦɨɱɟɜɢɧɚ 8 Ɇ, ɬɢɨɦɨɱɟɜɢɧɚ 2 Ɇ, CHAPS 4%, ɞɢɬɢɨɬɪɟɢɬɨɥ 1%, Ɍɪɢɫ 20 ɦɆ) ɢɡ ɪɚɫɱɟɬɚ 7 ɦɥ ɛɭɮɟɪɚ ɧɚ 1 ɝ ɩɨɪɨɲɤɚ. Ȼɭɮɟɪ ɝɨɬɨɜɢɥɢ ɡɚɪɚɧɟɟ, ɮɢɥɶɬɪɨɜɚɥɢ ɱɟɪɟɡ ɮɢɥɶɬɪ ɫ ɞɢɚɦɟɬɪɨɦ ɩɨɪ 0,22 ɦɤɦ ɢ ɯɪɚɧɢɥɢ ɞɨ ɢɫɩɨɥɶɡɨɜɚɧɢɹ ɜ ɚɥɢɤɜɨɬɚɯ ɩɪɢ –80°ɋ. ɇɟɩɨɫɪɟɞɫɬɜɟɧɧɨ ɩɟɪɟɞ ɞɨɛɚɜɥɟɧɢɟɦ ɛɭɮɟɪɚ ɤ ɨɛɪɚɡɰɭ ɤ ɧɟɦɭ ɞɨɛɚɜɥɹɥɢ ɤɨɤɬɟɣɥɶ ɢɡ ɢɧɝɢɛɢɬɨɪɨɜ ɩɪɨɬɟɚɡ (ɢɡ ɪɚɫɱɟɬɚ 1 ɦɤɥ/ɦɥ ɪɚɫɬɜɨɪɚ ɨɪɬɨɜɚɧɚɞɚɬɚ ɧɚɬɪɢɹ 1 Ɇ, 1 ɦɤɥ/ɦɥ ɪɚɫɬɜɨɪɚ ɚɩɪɨɬɢɧɢɧɚ 10 ɦɝ/ɦɥ, 2 ɦɤɥ/ɦɥ ɪɚɫɬɜɨɪɚ ɮɟɧɢɥɦɟɬɢɥɫɭɥɶɮɨɧɢɥɮɥɸɨɪɢɞɚ 0,5 Ɇ, 2 ɦɤɥ/ɦɥ ɪɚɫɬɜɨɪɚ ɥɟɭɩɟɩɬɢɧɚ 1 ɦɝ/ɦɥ, 2 ɦɤɥ/ɦɥ ɪɚɫɬɜɨɪɚ ɛɟɧɡɚɦɢɞɢɧɚ 100 ɦɆ). ɗɤɫɬɪɚɤɰɢɸ ɛɟɥɤɨɜ ɩɪɨɜɨɞɢɥɢ ɜ ɬɟɱɟɧɢɟ 1 ɱɚɫɚ ɩɪɢ ɧɟɩɪɟ41 ɪɵɜɧɨɦ ɩɟɪɟɦɟɲɢɜɚɧɢɢ ɧɚ ɲɟɣɤɟɪɟ ɩɪɢ ɤɨɦɧɚɬɧɨɣ ɬɟɦɩɟɪɚɬɭɪɟ. ɉɨ ɨɤɨɧɱɚɧɢɢ ɷɤɫɬɪɚɤɰɢɢ ɨɛɪɚɡɰɵ ɰɟɧɬɪɢɮɭɝɢɪɨɜɚɥɢ ɩɪɢ 15000 g ɩɪɢ ɤɨɦɧɚɬɧɨɣ ɬɟɦɩɟɪɚɬɭɪɟ ɜ ɬɟɱɟɧɢɟ 30 ɦɢɧɭɬ, ɨɬɛɢɪɚɥɢ ɫɭɩɟɪɧɚɬɚɧɬ ɢ ɯɪɚɧɢɥɢ ɩɪɢ –80°ɋ ɞɨ ɩɪɨɜɟɞɟɧɢɹ 2D ɷɥɟɤɬɪɨɮɨɪɟɡɚ. ȼɨ ɜɬɨɪɨɦ ɦɟɬɨɞɟ ɩɨɪɨɲɨɤ ɪɚɫɬɜɨɪɹɥɢ ɜ ɥɟɞɹɧɨɦ Ripa-ɛɭɮɟɪɟ pH=8,0 (Ɍɪɢɫ 50 ɦɆ, ɧɚɬɪɢɹ ɯɥɨɪɢɞ 150 ɦɆ, Ɍɪɢɬɨɧ X-100 1%, ɞɟɡɨɤɫɢɯɨɥɚɬ ɧɚɬɪɢɹ 1%, ɞɨɞɟɰɢɥɫɭɥɶɮɚɬ ɧɚɬɪɢɹ 0,1%). ɇɟɩɨɫɪɟɞɫɬɜɟɧɧɨ ɩɟɪɟɞ ɞɨɛɚɜɥɟɧɢɟɦ ɛɭɮɟɪɚ ɤ ɨɛɪɚɡɰɭ ɤ ɧɟɦɭ ɞɨɛɚɜɥɹɥɢ ɜɵɲɟɨɩɢɫɚɧɧɵɣ ɤɨɤɬɟɣɥɶ ɢɡ ɢɧɝɢɛɢɬɨɪɨɜ ɩɪɨɬɟɚɡ. Ƚɨɦɨɝɟɧɢɡɚɰɢɸ ɨɛɪɚɡɰɨɜ ɜ ɛɭɮɟɪɟ ɜɵɩɨɥɧɹɥɢ ɧɚ ɝɨɦɨɝɟɧɢɡɚɬɨɪɟ ɬɤɚɧɟɣ Tissue Tearor (Biospec Products, ɋɒȺ) ɩɪɢ 5–10000 ɨɛ./ɦɢɧ. 3 ɪɚɡɚ ɩɨ 10 ɫɟɤɭɧɞ ɫ ɩɨɫɥɟɞɭɸɳɟɣ ɦɹɝɤɨɣ ɫɨɧɢɮɢɤɚɰɢɟɣ ɩɪɢ 30% ɦɚɤɫɢɦɚɥɶɧɨɣ ɦɨɳɧɨɫɬɢ 3 ɪɚɡɚ ɩɨ 10 ɫ; ɨɩɟɪɚɰɢɢ ɜɵɩɨɥɧɹɥɢ ɧɚ ɥɶɞɭ. ɉɨ ɨɤɨɧɱɚɧɢɢ ɝɨɦɨɝɟɧɢɡɚɰɢɢ ɨɛɪɚɡɰɵ ɰɟɧɬɪɢɮɭɝɢɪɨɜɚɥɢ ɩɪɢ 15000 g ɩɪɢ ɤɨɦɧɚɬɧɨɣ ɬɟɦɩɟɪɚɬɭɪɟ 4°ɋ ɜ ɬɟɱɟɧɢɟ 30 ɦɢɧ., ɨɬɛɢɪɚɥɢ ɫɭɩɟɪɧɚɬɚɧɬ ɢ ɯɪɚɧɢɥɢ ɩɪɢ – 80°ɋ ɞɨ ɩɪɨɜɟɞɟɧɢɹ 2D ɷɥɟɤɬɪɨɮɨɪɟɡɚ. Ʉɨɧɰɟɧɬɪɚɰɢɸ ɛɟɥɤɚ ɜ ɷɤɫɬɪɚɤɬɚɯ ɨɩɪɟɞɟɥɹɥɢ ɩɨ Lowry. 2.6. ɉɪɢɝɨɬɨɜɥɟɧɢɟ ɢ ɨɩɬɢɦɢɡɚɰɢɹ ɨɛɪɚɡɰɨɜ ɞɥɹ ɢɫɫɥɟɞɨɜɚɧɢɹ Ⱦɥɹ ɜɵɞɟɥɟɧɢɹ ɛɟɥɤɨɜ ɢɡ ɤɥɟɬɨɤ ɢɫɩɨɥɶɡɨɜɚɥɨɫɶ ɪɚɡɪɭɲɟɧɢɟ ɤɥɟɬɨɱɧɵɯ ɦɟɦɛɪɚɧ ɫ ɩɨɦɨɳɶɸ ɨɛɪɚɛɨɬɤɢ ɭɥɶɬɪɚɡɜɭɤɨɦ. Ⱦɥɹ ɭɫɩɟɲɧɵɯ ɢɫɫɥɟɞɨɜɚɧɢɣ ɩɪɨɬɟɨɦɚ ɢɫɤɥɸɱɢɬɟɥɶɧɨ ɜɚɠɧɵɦ ɹɜɥɹɟɬɫɹ ɷɮɮɟɤɬɢɜɧɨɟ ɪɚɡɞɟɥɟɧɢɟ ɫɥɨɠɧɵɯ ɛɟɥɤɨɜɵɯ ɫɦɟɫɟɣ, ɩɨɡɜɨɥɹɸɳɟɟ ɜ ɞɚɥɶɧɟɣɲɟɦ ɩɪɨɜɨɞɢɬɶ ɚɧɚɥɢɡ ɛɟɥɤɨɜ, ɩɪɢɫɭɬɫɬɜɭɸɳɢɯ ɜ ɧɢɡɤɢɯ ɤɨɧɰɟɧɬɪɚɰɢɹɯ. ȼ ɫɜɹɡɢ ɫɨ ɫɥɨɠɧɨɫɬɶɸ ɰɟɥɵɯ ɩɪɨɬɟɨɦɨɜ ɢ ɪɚɡɧɨɨɛɪɚɡɢɟɦ ɛɟɥɤɨɜɵɯ ɫɜɨɣɫɬɜ, ɩɪɟɞɫɬɚɜɥɹɟɬɫɹ ɩɨɥɟɡɧɵɦ ɩɪɢɝɨɬɨɜɥɟɧɢɟ ɫɬɚɧɞɚɪɬɢɡɢɪɨɜɚɧɧɵɯ ɱɚɫɬɢɱɧɵɯ ɩɪɨɬɟɨɦɨɜ ɞɥɹ ɦɚɤɫɢɦɢɡɚɰɢɢ ɨɛɡɨɪɚ ɢ ɩɨɜɵɲɟɧɢɹ ɜɟɪɨɹɬɧɨɫɬɢ ɜɢɡɭɚɥɢɡɚɰɢɢ ɦɢɧɨɪɧɵɯ ɛɟɥɤɨɜ. 42 Ⱦɢɮɮɟɪɟɧɰɢɚɥɶɧɨɟ ɷɤɫɬɪɚɝɢɪɨɜɚɧɢɟ ɛɟɥɤɨɜ ɜ ɫɨɨɬɜɟɬɫɬɜɢɢ ɫ ɢɯ ɫɭɛɤɥɟɬɨɱɧɨɣ ɥɨɤɚɥɢɡɚɰɢɟɣ ɨɫɭɳɟɫɬɜɥɹɥɢ ɫ ɩɨɦɨɳɶɸ ɤɨɦɦɟɪɱɟɫɤɢ ɞɨɫɬɭɩɧɨɝɨ ɧɚɛɨɪɚ ɪɟɚɝɟɧɬɨɜ ProteoExtract® Subcellular Proteome Extraction Kit (S-PEK, Calbiochem, Germany). ɗɬɨɬ ɧɚɛɨɪ ɫɨɞɟɪɠɢɬ ɷɤɫɬɪɚɤɰɢɨɧɧɵɟ ɛɭɮɟɪɧɵɟ ɪɚɫɬɜɨɪɵ, ɩɪɢɝɨɬɨɜɥɟɧɧɵɟ ɫ ɢɫɩɨɥɶɡɨɜɚɧɢɟɦ ɫɨɟɞɢɧɟɧɢɣ ɜɵɫɨɤɨɣ ɱɢɫɬɨɬɵ, ɫɦɟɫɶ ɢɧɝɢɛɢɬɨɪɨɜ ɩɪɨɬɟɚɡ, ɩɪɟɞɨɬɜɪɚɳɚɸɳɢɯ ɪɚɡɪɭɲɟɧɢɟ ɛɟɥɤɨɜ, ɢ ɧɭɤɥɟɚɡɭ (Benzonase®), ɭɫɬɪɚɧɹɸɳɭɸ ɡɚɝɪɹɡɧɹɸɳɢɟ ɧɭɤɥɟɢɧɨɜɵɟ ɤɢɫɥɨɬɵ. Ɉɞɧɢɦ ɢɡ ɩɪɟɢɦɭɳɟɫɬɜ S-PEK ɹɜɥɹɟɬɫɹ ɜɨɡɦɨɠɧɨɫɬɶ ɢɡɛɢɪɚɬɟɥɶɧɨɝɨ ɢ ɦɹɝɤɨɝɨ, ɫɨɯɪɚɧɹɸɳɟɝɨ ɫɬɪɭɤɬɭɪɧɭɸ ɰɟɥɨɫɬɧɨɫɬɶ, ɷɤɫɬɪɚɝɢɪɨɜɚɧɢɹ ɤɨɦɩɨɧɟɧɬɨɜ ɫɭɛɤɥɟɬɨɱɧɵɯ ɫɬɪɭɤɬɭɪ ɫɩɟɰɢɚɥɶɧɵɦɢ ɫɦɟɫɹɦɢ ɪɟɚɝɟɧɬɨɜ. Ⱦɥɹ ɤɥɟɬɨɤ, ɜɵɪɚɳɟɧɧɵɯ ɜ ɫɭɫɩɟɧɡɢɢ, S-PEK ɧɚɱɢɧɚɟɬɫɹ ɫ ɦɹɝɤɨɝɨ ɨɫɚɠɞɟɧɢɹ ɢ ɩɪɨɦɵɜɚɧɢɹ ɤɥɟɬɨɤ. Ⱦɥɹ ɡɚɦɨɪɨɠɟɧɧɵɯ ɤɥɟɬɨɤ ɢ ɫɟɝɦɟɧɬɢɪɨɜɚɧɧɵɯ ɬɤɚɧɟɣ ɷɤɫɬɪɚɝɢɪɨɜɚɧɢɟ ɧɚɱɢɧɚɟɬɫɹ ɫ ɪɟɫɭɫɩɟɧɞɢɪɨɜɚɧɢɹ ɜ ɩɟɪɜɨɦ ɷɤɫɬɪɚɝɢɪɭɸɳɟɦ ɛɭɮɟɪɟ. Ɍɚɤɢɦ ɨɛɪɚɡɨɦ, ɰɟɥɵɣ ɩɪɨɬɟɨɦ ɩɪɟɜɪɚɳɚɟɬɫɹ ɜ ɫɭɛɩɪɨɬɟɨɦɵ ɦɟɧɶɲɟɣ ɫɥɨɠɧɨɫɬɢ ɜ ɨɬɧɨɲɟɧɢɢ ɫɜɨɟɝɨ ɫɨɫɬɚɜɚ. ɉɨɷɬɚɩɧɨɟ ɩɪɢɦɟɧɟɧɢɟ ɬɪɟɯ ɛɭɮɟɪɧɵɯ ɫɦɟɫɟɣ ɩɨɡɜɨɥɹɟɬ ɩɨɫɥɟɞɨɜɚɬɟɥɶɧɨ ɜɵɞɟɥɢɬɶ ɬɪɢ ɮɪɚɤɰɢɢ ɛɟɥɤɨɜ ɫ ɪɚɫɬɜɨɪɢɦɨɫɬɶɸ, ɢɡɦɟɧɹɸɳɟɣɫɹ ɨɬ ɦɚɤɫɢɦɚɥɶɧɨɣ ɤ ɦɢɧɢɦɚɥɶɧɨɣ. ɉɟɪɜɨɣ ɫɬɚɞɢɟɣ ɩɟɪɟɞ ɷɤɫɬɪɚɝɢɪɨɜɚɧɢɟɦ ɹɜɥɹɟɬɫɹ ɩɟɪɟɦɟɲɢɜɚɧɢɟ ɛɭɮɟɪɨɜ ɩɭɬɟɦ ɜɫɬɪɹɯɢɜɚɧɢɹ. ɉɪɨɰɟɞɭɪɚ ɧɚɱɢɧɚɟɬɫɹ ɫ ɨɫɬɨɪɨɠɧɨɝɨ ɭɞɚɥɟɧɢɹ ɩɢɬɚɬɟɥɶɧɨɣ ɫɪɟɞɵ, ɛɟɡ ɧɚɪɭɲɟɧɢɹ ɤɥɟɬɨɱɧɨɝɨ ɦɨɧɨɫɥɨɹ. Ɂɚɬɟɦ ɤɥɟɬɤɢ ɨɬɦɵɜɚɥɢ, ɨɫɬɨɪɨɠɧɨ ɧɚɧɨɫɹ ɧɚ ɦɨɧɨɫɥɨɣ 2 ɦɥ ɯɨɥɨɞɧɨɝɨ ɛɭɮɟɪɧɨɝɨ ɪɚɫɬɜɨɪɚ ɢ ɚɤɤɭɪɚɬɧɨ ɜɫɬɪɹɯɢɜɚɹ ɤɨɥɛɭ ɫ ɤɥɟɬɨɱɧɨɣ ɤɭɥɶɬɭɪɨɣ ɩɪɢ +4°C ɜ ɬɟɱɟɧɢɟ 5 ɦɢɧ. Ɂɚɬɟɦ ɩɪɨɦɵɜɨɱɧɵɣ ɛɭɮɟɪ ɩɨɥɧɨɫɬɶɸ ɭɞɚɥɹɟɬɫɹ, ɚ ɨɬɦɵɜɚɧɢɟ ɩɨɜɬɨɪɹɟɬɫɹ ɞɥɹ ɭɞɚɥɟɧɢɹ ɡɚɝɪɹɡɧɹɸɳɢɯ ɤɨɦɩɨɧɟɧɬɨɜ ɩɢɬɚɬɟɥɶɧɨɣ ɫɪɟɞɵ. Ⱦɚɥɟɟ ɫɦɟɲɢɜɚɥɢ 1 ɦɥ ɨɯɥɚɠɞɟɧɧɨɝɨ ɥɶɞɨɦ Extraction Buffer I ɢ 5 ɦɤɥ Protease Inhibitor Cocktail ɫ ɧɟɦɟɞɥɟɧɧɵɦ ɞɨɛɚɜɥɟɧɢɟɦ ɷɬɨɣ ɫɦɟɫɢ ɜ ɤɨɥɛɭ, ɧɟ ɧɚɪɭɲɚɹ ɤɥɟɬɨɱɧɨɝɨ ɦɨɧɨɫɥɨɹ, ɞɜɢɝɚɹ ɤɨɥɛɭ ɞɨ ɬɟɯ 43 ɩɨɪ, ɩɨɤɚ ɜɫɟ ɤɥɟɬɤɢ ɧɟ ɛɭɞɭɬ ɩɨɤɪɵɬɵ ɛɭɮɟɪɨɦ ɫ ɩɨɫɥɟɞɭɸɳɢɦ ɢɧɤɭɛɢɪɨɜɚɧɢɟɦ ɫɨɞɟɪɠɢɦɨɝɨ ɜ ɬɟɱɟɧɢɟ 10 ɦɢɧ ɩɪɢ ɨɫɬɨɪɨɠɧɨɦ ɜɫɬɪɹɯɢɜɚɧɢɢ. ɋɭɩɟɪɧɚɬɚɧɬ (ɮɪɚɤɰɢɹ 1) ɡɚɬɟɦ ɩɟɪɟɧɨɫɢɥɢ ɜ ɩɪɨɛɢɪɤɭ ɫ ɩɨɦɨɳɶɸ ɩɢɩɟɬɤɢ, ɧɟ ɧɚɪɭɲɚɹ ɤɥɟɬɨɱɧɨɝɨ ɫɥɨɹ. ȼɫɹ ɠɢɞɤɨɫɬɶ ɞɨɥɠɧɚ ɛɵɬɶ ɭɞɚɥɟɧɚ, ɚ ɮɪɚɤɰɢɹ 1 ɞɨɥɠɧɚ ɨɯɥɚɠɞɚɬɶɫɹ ɥɶɞɨɦ ɞɥɹ ɦɢɧɢɦɢɡɚɰɢɢ ɩɨɬɟɪɶ ɨɛɪɚɡɰɚ. Ɂɚɬɟɦ ɫɦɟɲɢɜɚɥɢ 1 ɦɥ ɨɯɥɚɠɞɟɧɧɨɝɨ ɷɤɫɬɪɚɤɰɢɨɧɧɨɝɨ ɛɭɮɟɪɚ 2 ɢ 5 ɦɤɥ Protease Inhibitor Cocktail ɢ ɧɟɦɟɞɥɟɧɧɨ ɩɟɪɟɧɨɫɢɥɢ ɫɦɟɫɶ ɜ ɤɨɥɛɭ, ɧɟ ɧɚɪɭɲɚɹ ɦɨɧɨɫɥɨɣ. ȼɫɟ ɤɥɟɬɤɢ ɧɚɤɪɵɜɚɥɢ ɛɭɮɟɪɧɵɦ ɪɚɫɬɜɨɪɨɦ ɢ ɢɧɤɭɛɢɪɨɜɚɥɢ ɜ ɬɟɱɟɧɢɟ 30 ɦɢɧ ɩɪɢ +4°C, ɫɥɟɝɤɚ ɜɫɬɪɹɯɢɜɚɹ. ɋɭɩɟɪɧɚɬɚɧɬ (ɮɪɚɤɰɢɹ 2) ɩɟɪɟɧɨɫɢɥɢ ɜ ɩɪɨɛɢɪɤɭ ɞɥɹ ɨɛɪɚɡɰɚ ɫ ɢɫɩɨɥɶɡɨɜɚɧɢɟɦ ɩɢɩɟɬɤɢ ɛɟɡ ɧɚɪɭɲɟɧɢɹ ɰɟɥɨɫɬɧɨɫɬɢ ɤɥɟɬɨɱɧɨɝɨ ɫɥɨɹ. Ɏɪɚɤɰɢɹ 2 ɫ ɭɞɚɥɟɧɧɨɣ ɢɡ ɧɟɟ ɠɢɞɤɨɫɬɶɸ ɯɪɚɧɢɬɫɹ ɡɚɬɟɦ ɧɚ ɥɶɞɭ. ɋɦɟɲɢɜɚɥɢ 500 ɦɤɥ ɨɯɥɚɠɞɟɧɧɨɝɨ ɷɤɫɬɪɚɤɰɢɨɧɧɨɝɨ ɛɭɮɟɪɚ III ɫ 5 ɦɤɥ ɤɨɤɬɟɣɥɹ ɢɧɝɢɛɢɬɨɪɚ ɩɪɨɬɟɚɡ ɢ 1,5 ɦɤɥ ( 375 U) ɛɟɧɡɨɧɚɡɵ. ɋɪɚɡɭ ɩɨɫɥɟ ɷɬɨɝɨ ɫɦɟɫɶ ɩɟɪɟɧɨɫɢɥɢ ɜ ɤɨɥɛɭ, ɧɟ ɧɚɪɭɲɚɹ ɦɨɧɨɫɥɨɹ ɢ ɨɫɬɨɪɨɠɧɨ ɞɜɢɝɚɹ ɤɨɥɛɭ, ɱɬɨɛɵ ɤɥɟɬɤɢ ɛɵɥɢ ɩɨɤɪɵɬɵ ɛɭɮɟɪɨɦ, ɡɚɬɟɦ ɢɧɤɭɛɢɪɨɜɚɥɢ ɢɯ ɩɪɢ ɨɫɬɨɪɨɠɧɨɦ ɜɫɬɪɹɯɢɜɚɧɢɢ ɜ ɬɟɱɟɧɢɟ 10 ɦɢɧ ɩɪɢ ɬɟɦɩɟɪɚɬɭɪɟ 4°C, ɞɨɫɬɢɝɚɹ ɨɩɬɢɦɚɥɶɧɨɣ ɩɪɟɰɢɩɢɬɚɰɢɢ. ɋɭɩɟɪɧɚɬɚɧɬ (ɮɪɚɤɰɢɹ 3) ɩɟɪɟɧɨɫɢɥɢ ɜ ɩɪɨɛɢɪɤɭ ɞɥɹ ɨɛɪɚɡɰɚ ɫ ɢɫɩɨɥɶɡɨɜɚɧɢɟɦ ɩɢɩɟɬɤɢ ɛɟɡ ɧɚɪɭɲɟɧɢɹ ɰɟɥɨɫɬɧɨɫɬɢ ɤɥɟɬɨɱɧɨɝɨ ɫɥɨɹ ɢ ɫ ɩɨɥɧɵɦ ɭɞɚɥɟɧɢɟɦ ɜɫɟɣ ɠɢɞɤɨɫɬɢ. Ʉɨɧɟɱɧɵɣ ɷɬɚɩ – ɫɦɟɲɢɜɚɧɢɟ ɩɪɢ ɤɨɦɧɚɬɧɨɣ ɬɟɦɩɟɪɚɬɭɪɟ 500 ɦɤɥ ɷɤɫɬɪɚɤɰɢɨɧɧɨɝɨ ɛɭɮɟɪɚ IV and 5 ɦɤɥ ɤɨɤɬɟɣɥɹ ɢɧɝɢɛɢɬɨɪɚ ɩɪɨɬɟɚɡ, ɩɟɪɟɧɨɫ ɫɦɟɫɢ ɜ ɤɨɥɛɭ ɞɥɹ ɡɚɜɟɪɲɟɧɢɹ ɫɨɥɸɛɢɥɢɡɚɰɢɢ ɨɫɬɚɬɨɱɧɨɝɨ ɦɚɬɟɪɢɚɥɚ, ɩɟɪɟɧɨɫ ɷɤɫɬɪɚɤɬɚ ɜ ɩɪɨɛɢɪɤɭ (ɮɪɚɤɰɢɹ 4) ɢ ɯɪɚɧɟɧɢɟ ɟɟ ɧɚ ɥɶɞɭ. ȿɫɥɢ ɷɤɫɩɟɪɢɦɟɧɬ ɩɪɨɜɨɞɢɬɫɹ ɧɟ ɫɪɚɡɭ, ɚ ɩɪɟɞɩɨɥɚɝɚɟɬɫɹ ɞɥɢɬɟɥɶɧɨɟ ɯɪɚɧɟɧɢɟ, ɚɥɢɤɜɨɬɵ (ɧɚɩɪɢɦɟɪ, 100 ɦɤɥ) ɯɪɚɧɹɬɫɹ ɩɪɢ ɬɟɦɩɟɪɚɬɭɪɟ –20°C ɢɥɢ ɛɨɥɟɟ ɧɢɡɤɨɣ. 44 ɇɚ ɫɥɟɞɭɸɳɟɣ ɩɨɫɥɟ ɷɤɫɬɪɚɝɢɪɨɜɚɧɢɹ ɫɬɚɞɢɢ ɪɚɛɨɬɵ ɩɪɢɦɟɧɹɟɬɫɹ ɧɚɛɨɪ ɪɟɚɝɟɧɬɨɜ 2D Clean-Up Kit (Amersham Biosciences), ɡɚɜɟɪɲɚɸɳɢɣ ɢ ɨɩɬɢɦɢɡɢɪɭɸɳɢɣ ɩɨɞɝɨɬɨɜɤɭ ɨɛɪɚɡɰɨɜ ɤ ɞɜɭɦɟɪɧɨɦɭ ɝɟɥɶɷɥɟɤɬɪɨɮɨɪɟɡɭ. Ɋɟɚɝɟɧɬɵ ɷɬɨɝɨ ɧɚɛɨɪɚ ɤɨɥɢɱɟɫɬɜɟɧɧɨ ɨɫɚɠɞɚɸɬ ɛɟɥɤɢ, ɨɫɬɚɜɥɹɹ ɩɨɦɟɯɨɨɛɪɚɡɭɸɳɢɟ ɫɨɟɞɢɧɟɧɢɹ (ɞɟɬɟɪɝɟɧɬɵ, ɫɨɥɢ, ɥɢɩɢɞɵ, ɮɟɧɨɥɵ, ɧɭɤɥɟɢɧɨɜɵɟ ɤɢɫɥɨɬɵ) ɜ ɪɚɫɬɜɨɪɟɧɧɨɦ ɫɨɫɬɨɹɧɢɢ. Ɉɫɚɞɨɤ ɨɬɞɟɥɹɟɬɫɹ ɰɟɧɬɪɢɮɭɝɢɪɨɜɚɧɢɟɦ, ɨɬɦɵɜɚɟɬɫɹ ɢ ɪɟɫɭɫɩɟɧɞɢɪɭɟɬɫɹ ɜ ɞɟɧɚɬɭɪɢɪɭɸɳɟɦ ɪɚɫɬɜɨɪɟ ɞɥɹ ɨɞɧɨɦɟɪɧɨɝɨ ɢɡɨɷɥɟɤɬɪɢɱɟɫɤɨɝɨ ɮɨɤɭɫɢɪɨɜɚɧɢɹ (ɂɗɎ). ɉɟɪɜɵɣ ɷɬɚɩ ɨɱɢɫɬɤɢ ɜɤɥɸɱɚɟɬ ɩɟɪɟɧɨɫ ɨɛɪɚɡɰɚ ɜ ɩɪɨɛɢɪɤɭ ɞɥɹ ɰɟɧɬɪɢɮɭɝɢɪɨɜɚɧɢɹ ɩɪɢ 8000 g. Ɂɚɬɟɦ ɭɞɚɥɹɟɬɫɹ ɫɭɩɟɪɧɚɬɚɧɬ, ɧɟ ɧɚɪɭɲɚɹ ɰɟɥɨɫɬɧɨɫɬɢ ɨɫɚɞɤɚ, ɩɨɜɬɨɪɧɨ ɩɪɨɜɨɞɢɬɫɹ ɰɟɧɬɪɢɮɭɝɢɪɨɜɚɧɢɟ ɜ ɬɟɱɟɧɢɟ 1 ɦɢɧ ɢ ɫɧɨɜɚ ɭɞɚɥɹɸɬɫɹ ɨɫɬɚɬɤɢ ɫɭɩɟɪɧɚɬɚɧɬɚ. Ʉɨɧɟɱɧɚɹ ɫɬɚɞɢɹ – ɪɟɫɭɫɩɟɧɞɢɪɨɜɚɧɢɟ ɤɚɠɞɨɝɨ ɨɫɚɞɤɚ (ɫɝɭɫɬɤɚ) ɜ ɜɨɞɧɨɦ ɪɚɫɬɜɨɪɟ ɞɥɹ ɂɗɎ ɩɟɪɜɨɝɨ ɧɚɩɪɚɜɥɟɧɢɹ. Ɉɛɴɟɦ ɪɟɝɢɞɪɢɪɭɸɳɟɝɨ ɪɚɫɬɜɨɪɚ ɦɨɠɟɬ ɫɨɫɬɚɜɥɹɬɶ 1/20 ɱɚɫɬɶ ɨɬ ɨɛɴɟɦɚ ɨɪɢɝɢɧɚɥɶɧɨɝɨ ɨɛɪɚɡɰɚ. ɉɪɨɛɢɪɤɚ ɜɫɬɪɹɯɢɜɚɟɬɫɹ ɜ ɬɟɱɟɧɢɟ 30 ɫɟɤɭɧɞ, ɢɧɤɭɛɢɪɭɟɬɫɹ ɩɪɢ ɤɨɦɧɚɬɧɨɣ ɬɟɦɩɟɪɚɬɭɪɟ ɞɨ ɩɨɥɧɨɝɨ ɪɚɫɬɜɨɪɟɧɢɹ ɫɝɭɫɬɤɚ ɢ ɰɟɧɬɪɢɮɭɝɢɪɭɟɬɫɹ ɩɪɢ 8 000g ɜ ɬɟɱɟɧɢɟ 10 ɦɢɧ ɞɥɹ ɭɞɚɥɟɧɢɹ ɧɟɪɚɫɬɜɨɪɢɦɨɝɨ ɦɚɬɟɪɢɚɥɚ. ɋɭɩɟɪɧɚɬɚɧɬ ɦɨɠɟɬ ɩɨɞɜɟɪɝɚɬɶɫɹ ɧɟɩɨɫɪɟɞɫɬɜɟɧɧɨ ɂɗɎ ɢɥɢ ɩɟɪɟɧɨɫɢɬɶɫɹ ɜ ɞɪɭɝɭɸ ɩɪɨɛɢɪɤɭ ɞɥɹ ɯɪɚɧɟɧɢɹ ɩɪɢ –80ºC ɞɥɹ ɩɨɫɥɟɞɭɸɳɢɯ ɚɧɚɥɢɡɨɜ. 2.7. ɉɨɫɥɟɞɨɜɚɬɟɥɶɧɨɫɬɶ (ɚɥɝɨɪɢɬɦ) ɩɪɨɬɟɨɦɧɨɝɨ ɚɧɚɥɢɡɚ Ⱥɥɝɨɪɢɬɦ ɷɮɮɟɤɬɢɜɧɨɝɨ ɩɪɨɬɟɨɦɧɨɝɨ ɚɧɚɥɢɡɚ ɬɪɟɛɭɟɬ ɧɟ ɬɨɥɶɤɨ ɫɬɚɧɞɚɪɬɢɡɚɰɢɢ, ɧɨ ɢ ɚɜɬɨɦɚɬɢɡɚɰɢɢ ɛɨɥɶɲɢɧɫɬɜɚ ɫɜɨɢɯ ɫɬɚɞɢɣ. ɀɟɥɚɬɟɥɶɧɨ ɬɚɤɠɟ ɪɚɡɪɟɲɟɧɢɟ, ɩɨɡɜɨɥɹɸɳɟɟ ɢɞɟɧɬɢɮɢɰɢɪɨɜɚɬɶ ɦɚɤɫɢɦɚɥɶɧɨ ɜɨɡɦɨɠɧɨɟ ɤɨɥɢɱɟɫɬɜɨ ɛɟɥɤɨɜ. Ɋɚɡɧɵɟ ɷɬɚɩɵ ɚɥɝɨɪɢɬɦɚ ɞɨɥɠ- 45 ɧɵ ɛɵɬɶ ɫɨɜɦɟɫɬɢɦɵ ɞɪɭɝ ɫ ɞɪɭɝɨɦ ɞɥɹ ɢɫɤɥɸɱɟɧɢɹ ɨɲɢɛɨɤ ɨɩɟɪɚɬɨɪɨɜ ɢ ɩɪɢɞɚɧɢɹ ɩɪɨɰɟɫɫɭ ɯɚɪɚɤɬɟɪɢɫɬɢɤ ɜɨɫɩɪɨɢɡɜɨɞɢɦɨɫɬɢ ɩɪɢ ɜɵɫɨɤɨɣ ɩɪɨɢɡɜɨɞɢɬɟɥɶɧɨɫɬɢ. Ɍɪɟɛɭɟɬɫɹ ɬɚɤɠɟ ɨɩɪɟɞɟɥɢɬɶ ɫɬɚɪɬɨɜɵɟ ɛɚɡɨɜɵɟ ɩɚɪɚɦɟɬɪɵ ɛɟɥɤɨɜ ɞɨ ɧɚɱɚɥɚ ɤɭɥɶɬɢɜɢɪɨɜɚɧɢɹ ɤɥɟɬɨɤ, ɱɬɨ ɩɨɡɜɨɥɢɬ ɜ ɞɚɥɶɧɟɣɲɟɦ ɪɟɝɢɫɬɪɢɪɨɜɚɬɶ ɢɯ ɞɢɧɚɦɢɤɭ (ɞɟɝɪɚɞɚɰɢɸ ɢɥɢ ɦɨɞɢɮɢɤɚɰɢɸ). ɇɚɦɢ ɩɪɟɞɥɨɠɟɧɚ ɩɪɨɰɟɞɭɪɚ ɨɩɪɟɞɟɥɟɧɢɹ ɬ.ɧ. ɪɟɮɟɪɟɧɫɧɨɣ (ɷɬɚɥɨɧɧɨɣ) ɬɨɱɤɢ ɞɥɹ ɢɫɫɥɟɞɨɜɚɧɢɹ ȽɋɄ ɜ ɜɢɞɟ ɩɨɥɭɚɜɬɨɦɚɬɢɡɢɪɨɜɚɧɧɨɝɨ ɚɥɝɨɪɢɬɦɚ ɩɪɨɬɟɨɦɧɨɝɨ ɚɧɚɥɢɡɚ. Ʉɥɸɱɟɜɨɣ ɦɨɦɟɧɬ ɩɨɥɭɱɟɧɢɹ CD34+ ɤɥɟɬɨɤ ɢɡ ɨɛɪɚɡɰɚ ɩɭɩɨɜɢɧɧɨɣ ɤɪɨɜɢ – ɜɵɞɟɥɟɧɢɟ ɞɨɫɬɚɬɨɱɧɨɝɨ ɤɨɥɢɱɟɫɬɜɚ ɤɥɟɬɨɤ, ɧɟɨɛɯɨɞɢɦɵɯ ɞɥɹ ɚɧɚɥɢɡɚ, ɚ ɷɬɨ – ɦɢɧɢɦɭɦ ɞɜɚ ɦɢɥɥɢɨɧɚ ɤɥɟɬɨɤ. ȿɫɥɢ ɨɛɪɚɡɟɰ ɫɨɞɟɪɠɢɬ ɛɨɥɶɲɟɟ ɤɨɥɢɱɟɫɬɜɨ ɤɥɟɬɨɤ, ɟɝɨ ɪɚɡɛɚɜɥɹɸɬ ɞɨ ɦɢɧɢɦɚɥɶɧɨɝɨ ɡɧɚɱɟɧɢɹ ɫɨɞɟɪɠɚɧɢɹ ɤɥɟɬɨɤ. Ɇɵ ɩɨɞɱɟɪɤɢɜɚɟɦ ɜɚɠɧɨɫɬɶ ɫɨɯɪɚɧɟɧɢɹ ɫɬɚɧɞɚɪɬɢɡɢɪɨɜɚɧɧɨɝɨ ɤɨɥɢɱɟɫɬɜɚ ɨɛɪɚɡɰɚ, ɡɚɝɪɭɠɚɟɦɨɝɨ ɧɚ ɩɥɚɫɬɢɧɵ ɞɥɹ ɂɗɎ ɜ ɩɟɪɜɨɦ ɧɚɩɪɚɜɥɟɧɢɢ 2D. Ʉɨɥɢɱɟɫɬɜɨ ɢɦɟɧɧɨ ɜ ɞɜɚ ɦɢɥɥɢɨɧɚ ɤɥɟɬɨɤ ɛɵɥɨ ɨɩɪɟɞɟɥɟɧɨ ɦɟɬɨɞɨɦ ɩɪɨɛ ɢ ɨɲɢɛɨɤ ɢ ɩɪɢɡɧɚɧɨ ɭɞɨɜɥɟɬɜɨɪɢɬɟɥɶɧɵɦ ɞɥɹ ȽɋɄ ɩɨ ɤɪɢɬɟɪɢɸ ɪɚɡɞɟɥɟɧɢɹ ɛɟɥɤɨɜ ɧɚ ɝɟɥɟ ɢ ɞɨɫɬɨɜɟɪɧɨɣ ɢɞɟɧɬɢɮɢɤɚɰɢɢ ɛɟɥɤɨɜɵɯ ɩɹɬɟɧ. Ɉɞɧɢɦ ɢɡ ɷɥɟɦɟɧɬɨɜ ɧɨɜɢɡɧɵ ɜ ɢɡɭɱɟɧɢɢ ɫɬɜɨɥɨɜɵɯ ɤɥɟɬɨɤ ɹɜɥɹɟɬɫɹ ɩɪɟɞɥɚɝɚɟɦɨɟ ɧɚɦɢ ɮɪɚɤɰɢɨɧɢɪɨɜɚɧɢɟ ɨɛɪɚɡɰɚ ɞɨ ɩɪɨɬɟɨɦɧɨɝɨ ɚɧɚɥɢɡɚ. ɇɚɛɨɪ ɞɥɹ ɮɪɚɤɰɢɨɧɢɪɨɜɚɧɢɹ ɩɨɡɜɨɥɹɟɬ ɞɨɫɬɢɝɧɭɬɶ ɫɪɚɡɭ ɧɟɫɤɨɥɶɤɨ ɰɟɥɟɣ: ɥɢɡɢɪɨɜɚɬɶ ɤɥɟɬɤɢ, ɩɪɨɜɟɫɬɢ ɨɱɢɫɬɤɭ ɢ ɮɪɚɤɰɢɨɧɢɪɨɜɚɧɢɟ ɨɛɪɚɡɰɚ. Ɉɛɪɚɡɟɰ ɞɟɥɢɬɫɹ ɧɚ ɬɪɢ ɮɪɚɤɰɢɢ (ɢɥɢ ɱɟɬɵɪɟ) ɫ ɜɨɡɪɚɫɬɚɸɳɟɣ ɝɢɞɪɨɮɨɛɧɨɫɬɶɸ (ɫɧɢɠɚɸɳɟɣɫɹ ɪɚɫɬɜɨɪɢɦɨɫɬɶɸ). ɗɬɨ ɨɛɟɫɩɟɱɢɜɚɟɬ ɧɚɫ ɬɪɟɦɹ-ɱɟɬɵɪɶɦɹ ɩɨɪɰɢɹɦɢ ɤɥɟɬɨɱɧɨɝɨ ɫɨɞɟɪɠɢɦɨɝɨ ɢ ɩɨɡɜɨɥɹɟɬ ɪɚɡɞɟɥɢɬɶ ɛɟɥɤɢ ɫ ɭɥɭɱɲɟɧɧɨɣ ɫɬɟɩɟɧɶɸ ɧɚɞɟɠɧɨɫɬɢ. ȼɦɟɫɬɨ ɝɟɥɹ ɫ ɫɨɬɧɹɦɢ ɛɟɥɤɨɜɵɯ ɩɹɬɟɧ ɪɟɡɭɥɶɬɚɬɨɦ ɹɜɥɹɟɬɫɹ ɪɚɫɩɪɟɞɟɥɟɧɢɟ ɫɨɬɟɧ ɛɟɥɤɨɜɵɯ ɩɹɬɟɧ ɧɚ ɬɪɟɯ-ɱɟɬɵɪɟɯ ɝɟɥɹɯ. Ɋɚɡɪɟɲɟɧɢɟ 46 ɛɟɥɤɨɜɵɯ ɩɹɬɟɧ ɨɛɵɱɧɨ ɞɨɫɬɢɝɚɟɬɫɹ ɢɫɩɨɥɶɡɨɜɚɧɢɟɦ ɝɟɥɟɣ ɛɨɥɶɲɟɣ ɜɟɥɢɱɢɧɵ, ɨɞɧɚɤɨ ɫ ɧɢɦɢ ɬɪɭɞɧɟɟ ɪɚɛɨɬɚɬɶ ɢ ɨɧɢ ɛɨɥɟɟ ɩɨɞɜɟɪɠɟɧɵ ɪɚɡɪɵɜɭ. ɂɫɩɨɥɶɡɨɜɚɧɢɟ ɝɟɥɟɣ ɦɟɧɶɲɟɝɨ ɮɨɪɦɚɬɚ (4–12% ɝɪɚɞɢɟɧɬɧɵɣ ɉȺȺȽ Criterion XT, Bio-Rad) ɨɤɚɡɚɥɨɫɶ ɨɩɬɢɦɚɥɶɧɵɦ ɞɥɹ ɭɥɭɱɲɟɧɧɨɝɨ ɪɚɡɞɟɥɟɧɢɹ ɛɟɥɤɨɜ. 2.8. Ɋɚɡɞɟɥɟɧɢɟ ɛɟɥɤɨɜ ɫ ɩɨɦɨɳɶɸ ɞɜɭɦɟɪɧɨɝɨ ɝɟɥɶ-ɷɥɟɤɬɪɨɮɨɪɟɡɚ ɉɪɨɜɨɞɢɥɢ ɚɧɚɥɢɬɢɱɟɫɤɨɟ ɮɪɚɤɰɢɨɧɢɪɨɜɚɧɢɟ ɩɨ ɞɜɭɦ ɧɟɡɚɜɢɫɢɦɵɦ ɞɪɭɝ ɨɬ ɞɪɭɝɚ ɮɢɡɢɤɨ-ɯɢɦɢɱɟɫɤɢɦ ɫɜɨɣɫɬɜɚɦ ɩɨɥɢɩɟɩɬɢɞɧɵɯ ɰɟɩɟɣ, ɨɬɪɚɠɚɸɳɢɯ ɨɫɨɛɟɧɧɨɫɬɢ ɢɯ ɩɟɪɜɢɱɧɨɣ ɫɬɪɭɤɬɭɪɵ: ɂɗɎ ɨɛɟɫɩɟɱɢɜɚɟɬ ɮɪɚɤɰɢɨɧɢɪɨɜɚɧɢɟ ɩɨ pI; ɷɥɟɤɬɪɨɮɨɪɟɡ ɜ ɩɪɢɫɭɬɫɬɜɢɢ SDS ɨɛɟɫɩɟɱɢɜɚɟɬ ɪɚɡɞɟɥɟɧɢɟ ɩɨ ɦɨɥɟɤɭɥɹɪɧɵɦ ɜɟɫɚɦ. Ⱦɥɹ ɥɭɱɲɟɣ ɪɚɡɪɟɲɚɸɳɟɣ ɫɩɨɫɨɛɧɨɫɬɢ ɢɫɩɨɥɶɡɨɜɚɥɢɫɶ ɝɪɚɞɢɟɧɬɧɵɟ ɝɟɥɢ, ɬ.ɟ. ɪɚɡɦɟɪ ɩɨɪ ɦɚɬɪɢɤɫɚ ɫɧɢɠɚɥɫɹ ɩɨ ɧɚɩɪɚɜɥɟɧɢɸ ɤ ɧɢɡɭ ɝɟɥɹ ɞɥɹ ɡɚɞɟɪɠɚɧɢɹ ɛɟɥɤɨɜ ɦɟɧɶɲɟɝɨ ɪɚɡɦɟɪɚ. ɉɟɪɜɨɟ ɧɚɩɪɚɜɥɟɧɢɟ 2D ɩɪɢɦɟɧɹɟɬɫɹ ɞɥɹ ɪɚɡɞɟɥɟɧɢɹ ɛɟɥɤɨɜ ɜ ɫɨɨɬɜɟɬɫɬɜɢɢ ɫ ɢɯ ɡɚɪɹɞɨɦ. ɋ ɷɬɨɣ ɰɟɥɶɸ ɢɫɩɨɥɶɡɭɸɬɫɹ ɬ.ɧ. ɢɡɨɷɥɟɤɬɪɢɱɟɫɤɢɟ ɫɬɪɢɩɵ ɫ ɪɇ 3–11. ɉɪɨɬɨɤɨɥ ɢɡɨɷɥɟɤɬɪɢɱɟɫɤɨɝɨ ɮɨɤɭɫɢɪɨɜɚɧɢɹ ɛɟɥɤɨɜ ɛɵɥ ɨɩɬɢɦɢɡɢɪɨɜɚɧ ɞɨ ɩɹɬɢ ɩɨɫɥɟɞɨɜɚɬɟɥɶɧɵɯ ɫɬɚɞɢɣ: 1) ɡɚɝɪɭɡɤɚ ɧɚ 3 ɱɚɫ ɩɪɢ 200 ȼ, 2) ɩɨɫɬɟɩɟɧɧɨɟ ɭɜɟɥɢɱɟɧɢɟ ɧɚɩɪɹɠɟɧɢɹ ɞɨ 1000 ȼ ɜ ɬɟɱɟɧɢɟ 6 ɱɚɫ, 3) ɭɜɟɥɢɱɟɧɢɟ ɧɚɩɪɹɠɟɧɢɹ ɞɨ 8000 ȼ ɧɚ 3 ɱɚɫɚ (ɮɨɤɭɫɢɪɨɜɚɧɢɟ), ɜɵɞɟɪɠɢɜɚɧɢɟ ɩɪɢ 5090 ȼ ɜ ɬɟɱɟɧɢɟ 6 ɱɚɫ, 5) ɜɵɞɟɪɠɢɜɚɧɢɟ ɜ ɬɟɱɟɧɢɟ 5 ɦɢɧ ɩɪɢ 8000 ȼ (ɮɢɧɚɥɶɧɨɟ ɮɨɤɭɫɢɪɨɜɚɧɢɟ). 12–15 Ʉɜ/ɱɚɫ – ɨɩɬɢɦɚɥɶɧɨ ɞɥɹ ɞɨɫɬɢɠɟɧɢɹ ɯɨɪɨɲɟɝɨ ɪɚɡɞɟɥɟɧɢɹ ɜ ɩɟɪɜɨɦ ɧɚɩɪɚɜɥɟɧɢɢ ɞɥɹ ȽɋɄ. Ɇɚɤɫɢɦɚɥɶɧɨɟ ɧɚɩɪɹɠɟɧɢɟ ɞɥɹ ɫɬɚɞɢɣ 3 ɢ 5–8000 ȼ, ɞɥɹ ɨɛɪɚɡɰɨɜ ɫ ɜɵɫɨɤɨɣ ɩɪɨɜɨɞɢɦɨɫɬɶɸ ɢ ɧɢɡɤɢɦ ɫɨɩɪɨɬɢɜɥɟɧɢɟɦ ɞɨɫɬɚɬɨɱɧɨ 4000 ȼ. 47 ȼɬɨɪɨɟ ɧɚɩɪɚɜɥɟɧɢɟ 2D ɩɨɡɜɨɥɹɟɬ ɪɚɡɞɟɥɢɬɶ ɛɟɥɤɢ, ɢɦɟɸɳɢɟ ɪɚɡɧɵɣ ɦɨɥɟɤɭɥɹɪɧɵɣ ɜɟɫ. ɉȺȺȽ (Criterion XT, Bio-Rad) ɫ ɝɪɚɞɢɟɧɬɨɦ 4–12% ɩɨɡɜɨɥɹɟɬ ɪɚɡɞɟɥɢɬɶ ɛɟɥɤɢ ɫ ɦɨɥɟɤɭɥɹɪɧɵɦ ɜɟɫɨɦ ɨɬ 10 ɞɨ 200 kDa. 2.9. Ɉɤɪɚɲɢɜɚɧɢɟ (ɞɟɬɟɤɰɢɹ) ɢ ɜɢɡɭɚɥɢɡɚɰɢɹ ɛɟɥɤɨɜɵɯ ɩɹɬɟɧ Ⱦɥɹ ɨɤɪɚɲɢɜɚɧɢɹ ɛɟɥɤɨɜ ɢɫɩɨɥɶɡɨɜɚɥɫɹ ɤɭɦɚɫɫɢ-ɩɨɞɨɛɧɵɣ ɤɪɚɫɢɬɟɥɶ (Imperial™, ThermoFisher Scientific). Ɉɧ ɞɚɜɚɥ ɥɭɱɲɢɟ ɪɟɡɭɥɶɬɚɬɵ (ɱɭɜɫɬɜɢɬɟɥɶɧɨɫɬɶ 6 ɧɝ ɛɟɥɤɚ, ɢɡɛɢɪɚɬɟɥɶɧɨɫɬɶ), ɱɟɦ ɩɪɨɱɢɟ ɧɟɮɥɭɨɪɟɫɰɟɧɬɧɵɟ ɤɨɦɦɟɪɱɟɫɤɢ ɞɨɫɬɭɩɧɵɟ ɤɪɚɫɢɬɟɥɢ. Ʉɪɚɫɢɬɟɥɶ ɜɡɚɢɦɨɞɟɣɫɬɜɨɜɚɥ ɫ ɝɟɥɟɦ ɜ ɬɟɱɟɧɢɟ ɨɞɧɨɝɨ ɱɚɫɚ. Ⱦɥɹ ɩɨɜɵɲɟɧɢɹ ɤɨɧɬɪɚɫɬɧɨɫɬɢ ɝɟɥɶ ɡɚɬɟɦ ɨɛɪɚɛɚɬɵɜɚɥɢ ɜɨɞɨɣ MilliQ ɜ ɬɟɱɟɧɢɟ ɧɨɱɢ. Ȼɟɥɤɨɜɵɟ ɩɹɬɧɚ ɩɪɢɨɛɪɟɬɚɥɢ ɫɜɟɬɥɨ-ɩɭɪɩɭɪɧɵɣ ɰɜɟɬ ɢ ɱɟɬɤɨɫɬɶ, ɫɩɨɫɨɛɫɬɜɭɸɳɭɸ ɩɨɫɥɟɞɭɸɳɟɦɭ ɜɵɪɟɡɚɧɢɸ. ȼɢɡɭɚɥɢɡɚɰɢɹ ɨɤɪɚɲɟɧɧɵɯ ɝɟɥɟɣ ɩɪɨɜɨɞɢɥɚɫɶ ɫ ɩɨɦɨɳɶɸ ɩɪɢɛɨɪɚ Dyversity (Syngene). ɗɬɚ ɩɪɨɰɟɞɭɪɚ ɡɚɧɢɦɚɥɚ 1–2 ɦɢɧ. ɋɤɚɧɢɪɨɜɚɧɧɵɟ ɫɧɢɦɤɢ (ɢɡɨɛɪɚɠɟɧɢɹ) ɩɨɞɜɟɪɝɚɥɢɫɶ ɚɧɚɥɢɡɭ ɞɥɹ ɨɛɧɚɪɭɠɟɧɢɹ ɛɟɥɤɨɜɵɯ ɩɹɬɟɧ, ɱɬɨ ɩɨɡɜɨɥɹɥɨ ɩɪɨɜɨɞɢɬɶ ɢɯ ɜɵɪɟɡɚɧɢɟ ɢ ɢɞɟɧɬɢɮɢɤɚɰɢɸ ɛɟɥɤɨɜ. ɉɨɫɥɟ ɪɚɡɞɟɥɟɧɢɹ ɞɜɭɦɟɪɧɵɦ ɷɥɟɤɬɪɨɮɨɪɟɡɨɦ ɢ ɨɤɪɚɲɢɜɚɧɢɹ Ʉɭɦɚɫɫɢ R350 ɤɭɫɨɱɤɢ ɝɟɥɹ ɞɢɚɦɟɬɪɨɦ 1–1,5 ɦɦ, ɫɨɨɬɜɟɬɫɬɜɭɸɳɢɟ ɛɟɥɤɨɜɵɦ ɩɹɬɧɚɦ, ɜɵɪɟɡɚɥɢ. 2.10. Ⱥɧɚɥɢɡ ɢɡɨɛɪɚɠɟɧɢɣ ɢ ɢɞɟɧɬɢɮɢɤɚɰɢɹ ɛɟɥɤɨɜ Ⱦɥɹ ɞɟɬɟɤɬɢɪɨɜɚɧɢɹ ɛɟɥɤɨɜɵɯ ɩɹɬɟɧ ɢ ɤɨɦɩɶɸɬɟɪɧɨɝɨ ɚɧɚɥɢɡɚ ɢɡɨɛɪɚɠɟɧɢɣ ɢɫɩɨɥɶɡɨɜɚɥɚɫɶ ɩɪɨɝɪɚɦɦɚ 2D Evolution/SameSpots (Nonlinear Dynamics). Ʉɨɦɩɶɸɬɟɪɧɵɣ ɚɧɚɥɢɡ ɩɪɢɦɟɧɹɥɫɹ ɬɚɤɠɟ ɞɥɹ ɫɪɚɜɧɟɧɢɹ ɪɚɡɧɵɯ ɝɟɥɟɣ, ɩɪɟɞɫɬɚɜɥɹɸɳɢɯ ɪɚɡɧɵɟ ɨɛɪɚɡɰɵ ɤɥɟɬɨɱɧɨɝɨ ɫɨɞɟɪɠɢɦɨɝɨ ɜ ɫɨɱɟɬɚɧɢɢ ɫɨ ɫɤɚɧɟɪɨɦ ɜɵɫɨɤɨɝɨ ɪɚɡɪɟɲɟɧɢɹ (UMAX scanner) ɢ/ɢɥɢ ɩɪɢɛɨɪɚ ɞɥɹ ɜɢɡɭɚɥɢɡɚɰɢɢ Dyversity (Syngene). 48 Ⱦɥɹ ɢɞɟɧɬɢɮɢɤɚɰɢɢ ɩɹɬɟɧ ɢɯ ɜɵɪɟɡɚɥɢ (ɜɪɭɱɧɭɸ ɢɥɢ ɚɜɬɨɦɚɬɢɱɟɫɤɢ ɫ ɩɨɦɨɳɶɸ Gelpix, Genetix) ɫ ɩɨɫɥɟɞɭɸɳɟɣ ɬɪɢɩɫɢɧɢɡɚɰɢɟɣ. ɉɨɥɭɱɟɧɧɵɟ ɩɟɩɬɢɞɵ ɚɧɚɥɢɡɢɪɨɜɚɥɢɫɶ ɧɚ MALDI ɦɚɫɫ-ɫɩɟɤɬɪɨɦɟɬɪɟ (MicroMass). ɂɞɟɧɬɢɮɢɤɚɰɢɸ ɛɟɥɤɨɜ ɩɨ «ɩɟɩɬɢɞɧɨɦɭ ɮɢɧɝɟɪɩɪɢɧɬɭ» ɨɫɭɳɟɫɬɜɥɹɥɢ ɩɪɢ ɩɨɦɨɳɢ ɩɪɨɝɪɚɦɦɵ Mascot ɜ ɛɚɡɟ ɞɚɧɧɵɯ NCBI ɫ ɭɱɟɬɨɦ ɜɨɡɦɨɠɧɨɝɨ ɨɤɢɫɥɟɧɢɹ ɦɟɬɢɨɧɢɧɨɜ ɤɢɫɥɨɪɨɞɨɦ ɜɨɡɞɭɯɚ ɢ ɦɨɞɢɮɢɤɚɰɢɢ ɰɢɫɬɟɢɧɨɜ ɚɤɪɢɥɚɦɢɞɨɦ. 2.11. Ⱥɧɚɥɢɡ ɞɜɭɦɟɪɧɵɯ ɝɟɥɟɣ Ⱥɧɚɥɢɡ ɝɟɥɟɜɵɯ ɢɡɨɛɪɚɠɟɧɢɣ ɛɟɥɤɚ (ɪɢɫ. 2.2) ɩɪɨɢɡɜɨɞɢɥɫɹ ɩɪɢ ɢɫɩɨɥɶɡɨɜɚɧɢɢ ɩɪɨɝɪɚɦɦɧɨɝɨ ɨɛɟɫɩɟɱɟɧɢɹ SameSpots (Nonlinear Dynamics). ɗɬɚ ɩɪɨɝɪɚɦɦɚ ɩɨɡɜɨɥɹɟɬ ɨɛɧɚɪɭɠɢɬɶ ɤɚɠɞɨɟ ɢɧɞɢɜɢɞɭɚɥɶɧɨɟ ɩɹɬɧɨ, ɩɪɢɫɜɨɢɬɶ ɟɦɭ ɧɨɦɟɪ ɢ ɤɨɥɢɱɟɫɬɜɟɧɧɨ ɨɰɟɧɢɬɶ ɜ ɬɟɪɦɢɧɚɯ ɰɜɟɬɨɜɨɣ ɢɧɬɟɧɫɢɜɧɨɫɬɢ. Ⱦɥɹ ɰɟɥɟɣ ɤɚɪɬɢɪɨɜɚɧɢɹ ɩɪɨɬɟɨɦɚ ȽɋɄ ɤɨɥɢɱɟɫɬɜɟɧɧɚɹ ɨɰɟɧɤɚ ɢɧɬɟɧɫɢɜɧɨɫɬɢ ɨɤɪɚɲɢɜɚɧɢɹ (ɞɪɭɝɢɦɢ ɫɥɨɜɚɦɢ – ɨɰɟɧɤɚ ɤɨɥɢɱɟɫɬɜɚ ɛɟɥɤɚ) ɧɟ ɹɜɥɹɟɬɫɹ ɨɛɹɡɚɬɟɥɶɧɨɣ. Ʉɨɥɢɱɟɫɬɜɟɧɧɵɣ ɚɧɚɥɢɡ ɛɟɥɤɨɜ ɩɨɥɟɡɟɧ ɞɥɹ ɪɚɡɞɟɥɟɧɢɹ ɩɹɬɟɧ ɢ ɞɥɹ ɨɩɪɟɞɟɥɟɧɢɹ ɩɪɟɞɟɥɨɜ ɱɭɜɫɬɜɢɬɟɥɶɧɨɫɬɢ ɞɥɹ ɪɚɡɧɵɯ ɛɟɥɤɨɜɵɯ ɤɪɚɫɢɬɟɥɟɣ. 2.12. ȼɵɪɟɡɚɧɢɟ ɛɟɥɤɨɜɵɯ ɩɹɬɟɧ ɗɬɚ ɩɪɨɰɟɞɭɪɚ ɛɵɥɚ ɚɜɬɨɦɚɬɢɡɢɪɨɜɚɧɚ ɢ ɨɫɭɳɟɫɬɜɥɹɥɚɫɶ ɫ ɩɨɦɨɳɶɸ ɪɨɛɨɬɚ Gelpix (Genetix). ɋɩɢɫɨɤ ɩɹɬɟɧ ɞɥɹ ɜɵɪɟɡɚɧɢɹ ɫɨɡɞɚɟɬɫɹ ɧɚ ɫɬɚɞɢɢ ɚɧɚɥɢɡɚ ɢɡɨɛɪɚɠɟɧɢɣ ɛɟɥɤɨɜɵɯ ɝɟɥɟɣ. Ʉɚɠɞɨɟ ɜɵɪɟɡɚɧɧɨɟ ɩɹɬɧɨ ɢɦɟɟɬ ɞɢɚɦɟɬɪ 2 ɦɦ ɢ ɜɵɫɨɬɭ, ɫɨɨɬɜɟɬɫɬɜɭɸɳɭɸ ɝɥɭɛɢɧɟ ɝɟɥɹ. ɉɨɫɥɟ ɜɵɪɟɡɚɧɢɹ ɩɹɬɧɨ ɩɟɪɟɧɨɫɢɬɫɹ ɧɚ 96-ɹɱɟɟɱɧɭɸ ɩɥɚɫɬɢɧɭ (ɩɥɚɲɤɭ) ɢ ɩɨɤɪɵɜɚɟɬɫɹ ɧɟɛɨɥɶɲɢɦ ɤɨɥɢɱɟɫɬɜɨɦ ɜɨɞɵ ɞɥɹ ɩɪɟɞɨɬɜɪɚɳɟɧɢɹ ɜɵɫɵɯɚɧɢɹ ɩɟɪɟɞ ɬɪɢɩɫɢɧɢɡɚɰɢɟɣ. Ɋɨɛɨɬ ɜɵɞɚɟɬ ɪɚɫɩɟɱɚɬɤɭ, ɫɜɹɡɵɜɚɸɳɭɸ ɧɨɦɟɪ ɩɹɬɧɚ ɫ ɧɨɦɟɪɨɦ ɹɱɟɣɤɢ. 49 Ⱦɥɹ ɩɨɜɵɲɟɧɢɹ ɷɮɮɟɤɬɢɜɧɨɫɬɢ ɪɚɛɨɬɵ ɪɨɛɨɬɚ ɫɨɫɬɚɜɥɹɟɬɫɹ ɫɩɟɰɢɚɥɶɧɚɹ ɤɨɨɪɞɢɧɚɬɧɚɹ ɤɚɪɬɚ, ɨɛɪɚɡɭɸɳɚɹ ɜ ɜɢɞɟ ɬɪɟɭɝɨɥɶɧɢɤɚ ɨɛɪɚɡ, ɚɧɚɥɢɡɢɪɭɟɦɵɣ ɫ ɩɨɦɨɳɶɸ ɤɨɦɩɶɸɬɟɪɧɨɣ ɩɪɨɝɪɚɦɦɵ (ɪɢɫ. 2.2) ɫ ɨɛɪɚɡɨɦ, ɩɪɨɢɡɜɨɞɢɦɵɦ ɜɵɪɟɡɚɸɳɢɦ ɪɨɛɨɬɨɦ. ɗɬɨ ɞɟɥɚɟɬɫɹ ɞɥɹ ɢɫɩɨɥɶɡɨɜɚɧɢɹ ɪɨɛɨɬɨɦ ɜɵɛɪɚɧɧɵɯ ɤɨɨɪɞɢɧɚɬ, ɫɨɨɬɜɟɬɫɬɜɭɸɳɢɯ ɤɚɠɞɨɦɭ ɢɧɞɢɜɢɞɭɚɥɶɧɨɦɭ ɩɹɬɧɭ. Ɋɢɫ. 2.2. Ɍɪɟɭɝɨɥɶɧɵɟ ɤɨɨɪɞɢɧɚɬɵ ɛɟɥɤɨɜɵɯ ɩɹɬɟɧ – ɩɹɬɧɚ ɜɵɪɟɡɚɸɬɫɹ ɜɧɭɬɪɢ ɩɥɨɳɚɞɢ ɬɪɟɭɝɨɥɶɧɢɤɚ. Ɂɧɚɤɨɦ ɏ ɩɨɦɟɱɟɧɵ ɜɵɪɟɡɚɧɧɵɟ ɩɹɬɧɚ 50 2.13. ɉɟɪɟɜɚɪɢɜɚɧɢɟ ɛɟɥɤɚ ɬɪɢɩɫɢɧɨɦ Ȼɟɡ ɩɟɪɟɜɚɪɢɜɚɧɢɹ ɬɪɢɩɫɢɧɨɦ ɧɟɜɨɡɦɨɠɧɨ ɩɪɢɫɜɨɟɧɢɟ ɛɟɥɤɭ ɢɞɟɧɬɢɮɢɤɚɰɢɨɧɧɨɝɨ ɧɨɦɟɪɚ (id). ȼ ɷɬɨɣ ɫɜɹɡɢ ɢɫɩɨɥɶɡɭɟɬɫɹ ɜɵɫɨɤɨɤɚɱɟɫɬɜɟɧɧɵɣ ɮɟɪɦɟɧɬ – ɬɪɢɩɫɢɧ (Promega), ɤɨɬɨɪɵɣ ɪɚɫɬɜɨɪɹɸɬ ɜ ɛɭɮɟɪɟ ɜ ɫɨɨɬɜɟɬɫɬɜɢɢ ɫ ɪɟɤɨɦɟɧɞɚɰɢɟɣ ɩɪɨɢɡɜɨɞɢɬɟɥɹ. ɉɨɷɬɚɩɧɚɹ ɩɪɨɰɟɞɭɪɚ ɩɟɪɟɜɚɪɢɜɚɧɢɹ ɬɪɢɩɫɢɧɨɦ ɩɨɡɜɨɥɹɟɬ ɷɤɫɬɪɚɝɢɪɨɜɚɬɶ ɦɚɤɫɢɦɚɥɶɧɨɟ ɤɨɥɢɱɟɫɬɜɨ ɛɟɥɤɚ ɢɡ ɜɵɪɟɡɚɧɧɨɝɨ ɫɬɨɥɛɢɤɚ ɝɟɥɹ. ɉɪɨɰɟɫɫ ɩɟɪɟɜɚɪɢɜɚɧɢɹ ɛɟɥɤɚ ɛɵɥ ɚɜɬɨɦɚɬɢɡɢɪɨɜɚɧ ɫ ɢɫɩɨɥɶɡɨɜɚɧɢɟɦ ɪɨɛɨɬɚ (GE healthcare). ɉɚɧɟɥɶ ɭɩɪɚɜɥɟɧɢɹ ɪɨɛɨɬɨɦ ɩɨɤɚɡɚɧɚ ɧɚ ɪɢɫ. 2.3. Ɋɢɫ. 2.3. ɉɚɧɟɥɶ ɭɩɪɚɜɥɟɧɢɹ ɪɨɛɨɬɨɦ ɩɟɪɟɜɚɪɢɜɚɧɢɹ ɛɟɥɤɚ 51 Ⱥɜɬɨɦɚɬɢɡɢɪɨɜɚɧɧɨɟ ɩɟɪɟɜɚɪɢɜɚɧɢɟ ɛɟɥɤɨɜ ɜɤɥɸɱɚɟɬ ɫɥɟɞɭɸɳɢɟ ɫɬɚɞɢɢ: 1) ɍɞɚɥɟɧɢɟ ɨɫɬɚɬɨɱɧɨɣ ɜɨɞɵ ɢɡ ɢɫɯɨɞɧɨɝɨ ɨɛɪɚɡɰɚ. 2) ɂɧɤɭɛɚɰɢɸ ɝɟɥɟɜɨɝɨ ɫɬɨɥɛɢɤɚ ɜ ɬɟɱɟɧɢɟ 20 ɦɢɧ ɚɦɢɧɨɛɢɤɚɪɛɨɧɚɬɨɦ-ɦɟɬɚɧɨɥɨɦ. 3) ɉɪɨɦɵɜɤɚ ɝɟɥɟɜɨɝɨ ɫɬɨɥɛɢɤɚ ɚɦɢɧɨɛɢɤɚɪɛɨɧɚɬɨɦ. 4) Ɉɛɟɡɜɨɠɢɜɚɧɢɟ ɫɬɨɥɛɢɤɚ ɜ ɬɟɱɟɧɢɟ 120 ɦɢɧ 60% ɪɚɫɬɜɨɪɨɦ ɚɰɟɬɨɧɢɬɪɢɥɚ. 5) ɍɞɚɥɟɧɢɟ ɨɫɬɚɬɤɨɜ ɠɢɞɤɨɫɬɢ ɢ ɜɵɫɭɲɢɜɚɧɢɟ ɜ ɬɟɱɟɧɢɟ 10 ɦɢɧ. 6) ɉɟɪɟɜɚɪɢɜɚɧɢɟ – ɞɨɛɚɜɥɟɧɢɟ 20 ɦɤɥ ɮɟɪɦɟɧɬɚ ɢ ɢɧɤɭɛɚɰɢɹ ɜ ɬɟɱɟɧɢɟ 360 ɦɢɧ. 2.14. Ɉɫɨɛɟɧɧɨɫɬɢ ɚɧɚɥɢɡɚ ɤɚɪɞɢɨɩɪɟɩɚɪɚɬɨɜ Ⱦɥɹ ɩɪɨɜɟɞɟɧɢɹ 2D ɷɥɟɤɬɪɨɮɨɪɟɡɚ ɩɪɟɩɚɪɚɬɨɜ ɢɡ ɚɨɪɬɵ 250 ɦɤɝ ɷɤɫɬɪɚɝɢɪɨɜɚɧɧɨɝɨ ɛɟɥɤɚ ɨɛɟɫɫɨɥɢɜɚɥɢ ɩɭɬɟɦ ɮɢɥɶɬɪɨɜɚɧɢɹ ɧɚ ɤɨɥɨɧɤɚɯ Spin-X (Costar). Ⱦɚɥɟɟ ɢɫɫɥɟɞɭɟɦɵɣ ɨɛɪɚɡɟɰ ɨɱɢɳɚɥɢ ɢ ɨɫɚɠɞɚɥɢ ɫ ɢɫɩɨɥɶɡɨɜɚɧɢɟɦ ɧɚɛɨɪɚ 2D-Clean-up (GE Healthcare) ɜ ɫɨɨɬɜɟɬɫɬɜɢɢ ɫ ɢɧɫɬɪɭɤɰɢɟɣ ɩɪɨɢɡɜɨɞɢɬɟɥɹ. ɉɨɫɥɟ ɨɛɟɫɫɨɥɢɜɚɧɢɹ ɨɛɪɚɡɰɵ ɪɟɫɭɫɩɟɧɞɢɪɨɜɚɥɢ ɜ ɪɟɝɢɞɪɚɬɢɪɭɸɳɟɦ ɛɭɮɟɪɟ. Ⱦɥɹ ɷɥɟɤɬɪɨɮɨɪɟɡɚ ɜ ɩɟɪɜɨɦ ɢɡɦɟɪɟɧɢɢ ɤ ɨɛɪɚɡɰɚɦ ɞɨɛɚɜɥɹɥɢ ɬɪɢɛɭɬɢɥɮɨɫɮɢɧ ɜ ɤɚɱɟɫɬɜɟ ɜɨɫɫɬɚɧɨɜɢɬɟɥɹ ɢ ɚɦɮɨɥɢɬɵ (Bio-Rad), ɷɥɟɤɬɪɨɮɨɪɟɡ ɩɪɨɜɨɞɢɥɢ ɜ ɩɨɥɢɚɤɪɢɥɚɦɢɞɧɵɯ ɫɬɪɢɩɚɯ ɫ ɮɢɤɫɢɪɨɜɚɧɧɵɦɢ ɝɪɚɞɢɟɧɬɚɦɢ pH 4–7 ɢ 3–10 (Bio-Rad). ɂɡɨɷɥɟɤɬɪɨɮɨɤɭɫɢɪɨɜɤɭ ɩɪɨɜɨɞɢɥɢ ɜ ɝɨɪɢɡɨɧɬɚɥɶɧɨɦ ɧɚɩɪɚɜɥɟɧɢɢ ɩɪɢ 20°ɋ, ɤɚɤ ɨɩɢɫɚɧɨ Lázaro ɢ ɫɨɚɜɬ. [55]. ȼɨ ɜɪɟɦɹ ɢɡɨɷɥɟɤɬɪɨɮɨɤɭɫɢɪɨɜɤɢ 2 ɩɨɥɨɫɤɢ ɮɢɥɶɬɪɨɜɚɥɶɧɨɣ ɛɭɦɚɝɢ ɢ ɩɨɥɢɚɤɪɢɥɚɦɢɞɧɵɟ ɫɬɪɢɩɵ ɛɵɥɢ ɩɨɦɟɳɟɧɵ ɦɟɠɞɭ ɷɥɟɤɬɪɨɞɚɦɢ (Electrode Wicks, Bio-Rad) ɞɥɹ ɭɞɚɥɟɧɢɹ ɫɨɥɟɣ, ɢɡɛɵɬɤɚ ɜɨɞɵ ɢ ɛɟɥɤɨɜ ɫ ɢɡɨɷɥɟɤ- 52 ɬɪɢɱɟɫɤɨɣ ɬɨɱɤɨɣ, ɧɚɯɨɞɹɳɟɣɫɹ ɜɧɟ ɩɨɝɪɚɧɢɱɧɵɯ ɡɧɚɱɟɧɢɣ pH ɞɥɹ ɢɫɩɨɥɶɡɭɸɳɢɯɫɹ ɩɨɥɢɚɤɪɢɥɚɦɢɞɧɵɯ ɫɬɪɢɩɨɜ. ɉɨ ɨɤɨɧɱɚɧɢɢ ɢɡɨɷɥɟɤɬɪɨɮɨɤɭɫɢɪɨɜɤɢ ɫɬɪɢɩɵ ɜɵɞɟɪɠɢɜɚɥɢ ɜ ɷɤɜɢɥɢɛɪɢɪɭɸɳɟɦ ɛɭɮɟɪɟ ɢ ɩɪɨɜɨɞɢɥɢ ɷɥɟɤɬɪɨɮɨɪɟɡ ɜɨ ɜɬɨɪɨɦ ɢɡɦɟɪɟɧɢɢ. Ɂɚɬɟɦ ɝɟɥɢ ɨɤɪɚɲɢɜɚɥɢ ɫɟɪɟɛɪɨɦ ɫ ɢɫɩɨɥɶɡɨɜɚɧɢɟɦ ɧɚɛɨɪɨɜ Ampholine PAGplate (Pharmacia Biotech, GE Healthcare) ɜ ɫɨɨɬɜɟɬɫɬɜɢɢ ɫ ɢɧɫɬɪɭɤɰɢɟɣ ɩɪɨɢɡɜɨɞɢɬɟɥɹ. Ɉɤɪɚɲɟɧɧɵɟ ɝɟɥɢ ɫɤɚɧɢɪɨɜɚɥɢ ɧɚ GS800 ɫɤɚɧɟɪɟ-ɞɟɧɫɢɬɨɦɟɬɪɟ (Bio-Rad) ɢ ɚɧɚɥɢɡɢɪɨɜɚɥɢ ɫ ɩɨɦɨɳɶɸ ɩɪɨɝɪɚɦɦɧɨɝɨ ɩɚɤɟɬɚ PDQUEST 8.0 (Bio-Rad). Ⱦɥɹ ɢɞɟɧɬɢɮɢɤɚɰɢɢ ɛɟɥɤɨɜ ɫɨɨɬɜɟɬɫɬɜɭɸɳɢɟ ɩɹɬɧɚ ɜɵɪɟɡɚɥɢ ɢɡ ɝɟɥɹ, ɩɟɪɟɜɚɪɢɜɚɥɢ ɧɚ ɚɜɬɨɦɚɬɟ Ettan Digester (GE Healthcare) ɢ ɩɪɨɜɨɞɢɥɢ ɨɩɪɟɞɟɥɟɧɢɟ ɦɟɬɨɞɨɦ MALDI-TOF/TOF ɢ ɩɨɢɫɤɨɦ ɫɨɨɬɜɟɬɫɬɜɢɣ ɜ ɛɚɡɟ ɞɚɧɧɵɯ. ȼɤɪɚɬɰɟ, ɮɪɚɝɦɟɧɬɵ ɝɟɥɹ ɜɨɫɫɬɚɧɚɜɥɢɜɚɥɢ 10 ɦɆ ɞɢɬɢɨɬɪɟɢɬɨɥɨɦ (Sigma Aldrich) ɜ 50 ɦɆ ɛɢɤɚɪɛɨɧɚɬɟ ɚɦɦɨɧɢɹ (Scharlau) ɢ ɚɥɤɢɥɢɪɨɜɚɥɢ 55 ɦɆ ɢɨɞɨɚɰɟɬɚɦɢɞɨɦ (Sigma Aldrich) in ɜ 50 ɦɆ ɛɢɤɚɪɛɨɧɚɬɟ ɚɦɦɨɧɢɹ. Ɏɪɚɝɦɟɧɬɵ ɝɟɥɹ ɨɬɦɵɜɚɥɢ ɜ ɜ 50 ɦɆ ɛɢɤɚɪɛɨɧɚɬɟ ɚɦɦɨɧɢɹ, 50% ɦɟɬɚɧɨɥɟ (Scharlau) ɢ ɚɰɟɬɨɧɢɬɪɢɥɟ (Scharlau), ɢ ɜɵɫɭɲɢɜɚɥɟ ɜ Speedvac (Thermo Fisher). Ɇɨɞɢɮɢɰɢɪɨɜɚɧɧɵɣ Modified ɫɜɢɧɨɣ ɬɪɢɩɫɢɧ (Promega, ɋɒȺ) ɞɨɛɚɜɥɹɥɢ ɤ ɮɪɚɝɦɟɧɬɚɦ ɝɟɥɹ ɜ ɤɨɧɟɱɧɨɣ ɤɨɧɰɟɧɬɪɚɰɢɢ 20 ɧɝ/ɦɤɥ ɜ 20 ɦɆ ɛɢɤɚɪɛɨɧɚɬɟ ɚɦɦɨɧɢɹ ɢ ɩɟɪɟɜɚɪɢɜɚɥɢ ɜ ɬɟɱɟɧɢɟ ɧɨɱɢ ɩɪɢ 37°C. ɇɚɤɨɧɟɰ, ɞɨɛɚɜɥɹɥɢ 60% ɜɨɞɧɵɣ ɪɚɫɬɜɨɪ ɚɰɟɬɨɧɢɬɪɢɥɚ ɫ 0,1% ɦɭɪɚɜɶɢɧɨɣ ɤɢɫɥɨɬɨɣ (Sigma Aldrich) ɞɥɹ ɩɨɥɧɨɣ ɷɤɫɬɪɚɤɰɢɢ ɩɟɩɬɢɞɨɜ. ɉɨ ɨɤɨɧɱɚɧɢɢ ɩɟɪɟɜɚɪɢɜɚɧɢɹ ɚɥɢɤɜɨɬɵ ɨɛɪɚɡɰɨɜ ɫɦɟɲɢɜɚɥɢ ɫ ɚɥɢɤɜɨɬɚɦɢ ɦɚɬɪɢɤɫɚ Į-ɰɢɚɧɨ-4-ɝɢɞɪɨɤɫɢɤɨɪɢɱɧɨɣ ɤɢɫɥɨɬɵ (Sigma Aldrich) ɜ 50% ɚɰɟɬɨɧɢɬɪɢɥɟ ɫ 0,1% ɬɪɢɮɬɨɪɭɤɫɭɫɧɨɣ ɤɢɫɥɨɬɨɣ. ɋɦɟɫɶ ɩɨɦɟɳɚɥɢ ɬɨɧɤɢɦ ɫɥɨɟɦ ɧɚ 123´81 ɦɦ Opti-TOF 384 Well MALDI plate (Applied Biosystems) ɢ ɜɵɫɭɲɢɜɚɥɢ ɩɪɢ ɤɨɦɧɚɬɧɨɣ 53 ɬɟɦɩɟɪɚɬɭɪɟ. Ⱦɚɧɧɵɟ MALDI-MS/MS ɩɨɥɭɱɚɥɢ ɚɜɬɨɦɚɬɢɱɟɫɤɢ ɩɪɢ ɦɚɫɫ-ɫɩɟɤɬɪɨɦɟɬɪɢɢ ɧɚ ɚɧɚɥɢɡɚɬɨɪɟ 4800 Plus MALDITOF/TOF Analyzer (Applied Biosystems). Ɇɚɫɫ-ɫɩɟɤɬɪɨɦɟɬɪ MALDI (MICROMASS) ɩɨɡɜɨɥɹɟɬ ɨɞɧɨɜɪɟɦɟɧɧɨɟ ɫɱɢɬɵɜɚɧɢɟ ɩɥɚɲɤɢ ɜ ɚɜɬɨɦɚɬɢɱɟɫɤɨɦ ɪɟɠɢɦɟ. 2.15. ɂɞɟɧɬɢɮɢɤɚɰɢɹ ɛɟɥɤɨɜ – MALDI Mass Spec ɋɩɟɤɬɪɵ ɩɨɥɭɱɚɥɢ ɜ ɪɟɠɢɦɟ ɨɬɪɚɠɟɧɢɹ (reflection mode), ɢɫɩɨɥɶɡɭɹ ɩɪɢɦɟɪɧɨ 150 ɥɚɡɟɪɧɵɯ ɜɵɫɬɪɟɥɨɜ ɩɨ ɜɫɟɣ ɩɥɨɳɚɞɢ ɦɢɲɟɧɢ (ɨɛɪɚɡɰɚ), ɢ ɚɧɚɥɢɡɢɪɨɜɚɥɢ, ɢɫɩɨɥɶɡɭɹ ɩɪɨɝɪɚɦɦɵ ɢ ɛɚɡɭ ɞɚɧɧɵɯ Mascot. ɉɟɪɟɜɚɪɟɧɧɵɣ ɛɟɥɨɤ ɧɚɧɨɫɢɬɫɹ ɧɚ ɩɥɚɫɬɢɧɭ ɦɚɫɫ-ɫɩɟɤɬɪɨɦɟɬɪɚ MALDI (MICROMASS). ɗɬɚ ɩɥɚɫɬɢɧɚ ɢɦɟɟɬ ɬɚɤɭɸ ɠɟ ɤɨɧɮɢɝɭɪɚɰɢɸ, ɤɚɤ ɢ 96ɹɱɟɟɟɱɧɚɹ ɩɥɚɲɤɚ ɞɥɹ ɩɪɹɦɨɣ ɢɧɬɟɪɩɨɥɹɰɢɢ ɢ ɨɩɪɟɞɟɥɟɧɢɹ id. Ɍɪɢɩɫɢɧ ɩɟɪɟɜɚɪɢɜɚɟɬ ɛɟɥɤɢ ɩɨ ɦɟɫɬɭ ɩɨɥɨɠɟɧɢɹ ɚɪɝɢɧɢɧɚ (R) ɢ ɥɢɡɢɧɚ (Ʉ), ɩɨɷɬɨɦɭ ɜɟɪɨɹɬɧɨɫɬɶ ɩɪɚɜɢɥɶɧɨɝɨ ɨɩɪɟɞɟɥɟɧɢɹ id ɛɟɥɤɚ ɡɚɜɢɫɢɬ ɨɬ ɧɚɥɢɱɢɹ ɷɬɢɯ ɚɦɢɧɨɤɢɫɥɨɬ ɢ ɫɩɨɫɨɛɧɨɫɬɢ ɮɟɪɦɟɧɬɚ ɪɚɫɩɨɡɧɚɜɚɬɶ ɭɤɚɡɚɧɧɵɟ ɦɟɫɬɚ. Ɇɚɫɫ-ɫɩɟɤɬɪɨɦɟɬɪ ɪɚɡɞɟɥɹɟɬ ɩɟɩɬɢɞɵ ɧɚ ɨɫɧɨɜɟ ɫɨɨɬɧɨɲɟɧɢɹ ɦɚɫɫɚ/ɡɚɪɹɞ (m/z), ɡɚɩɢɫɵɜɚɟɬ ɫɩɟɤɬɪ ɞɥɹ ɤɚɠɞɨɝɨ ɨɛɪɚɡɰɚ ɢ ɢɳɟɬ ɟɝɨ ɫɨɨɬɜɟɬɫɬɜɢɟ ɛɚɡɟ ɞɚɧɧɵɯ (Human, SwissProt). ȼɟɪɨɹɬɧɨɫɬɶ ɷɬɨɝɨ ɫɨɨɬɜɟɬɫɬɜɢɹ ɡɚɜɢɫɢɬ ɨɬ ɩɪɢɫɭɬɫɬɜɢɹ/ɨɬɫɭɬɫɬɜɢɹ ɩɟɩɬɢɞɚ ɜ ɫɩɟɤɬɪɟ ɢ ɬ.ɧ. ɩɟɪɟɤɪɵɬɢɹ (ɩɪɢɫɭɬɫɬɜɢɹ ɟɝɨ ɜ ɛɟɥɤɟ). ɂɞɟɧɬɢɮɢɤɚɰɢɹ ɛɟɥɤɨɜ, ɬɚɤɢɦ ɨɛɪɚɡɨɦ, ɪɚɫɫɦɚɬɪɢɜɚɟɬɫɹ ɤɚɤ ɪɟɡɭɥɶɬɚɬ ɤɨɦɩɶɸɬɟɪɧɨɝɨ ɩɨɢɫɤɚ ɩɨ ɛɚɡɚɦ ɞɚɧɧɵɯ ɨ ɫɟɤɜɟɧɢɪɨɜɚɧɧɵɯ ɩɨɫɥɟɞɨɜɚɬɟɥɶɧɨɫɬɹɯ (ɧɚɩɪɢɦɟɪ, NCBI) ɢ ɪɚɫɱɟɬɟ ɩɪɨɰɟɧɬɚ ɫɨɜɩɚɞɟɧɢɹ ɜɵɹɜɥɟɧɧɵɯ ɦɚɫɫ ɬɪɢɩɬɢɱɟɫɤɢɯ ɩɟɩɬɢɞɨɜ ɫ ɚɦɢɧɨɤɢɫɥɨɬɧɨɣ ɩɨɫɥɟɞɨɜɚɬɟɥɶɧɨɫɬɶɸ ɫɨɨɬɜɟɬɫɬɜɭɸɳɟɝɨ ɛɟɥɤɚ (% ɩɟɪɟɤɪɵɬɢɹ). 54 2.16. Ɉɛɴɟɞɢɧɟɧɢɟ ɞɚɧɧɵɯ, ɩɨɥɭɱɟɧɧɵɯ ɧɚ ɪɚɡɧɵɯ ɷɬɚɩɚɯ ɚɧɚɥɢɡɚ Ⱦɥɹ ɤɨɧɬɪɨɥɹ ɡɚ ɯɨɞɨɦ ɩɪɨɰɟɞɭɪɵ ɚɧɚɥɢɡɚ ɢɫɩɨɥɶɡɨɜɚɥɚɫɶ ɫɩɟɰɢɚɥɶɧɚɹ ɪɚɛɨɱɚɹ ɬɟɬɪɚɞɶ. ȼ ɧɟɟ ɜɧɨɫɢɥɢɫɶ ɪɟɡɭɥɶɬɢɪɭɸɳɢɟ ɞɚɧɧɵɟ ɤɚɠɞɨɣ ɫɬɚɞɢɢ ɚɧɚɥɢɡɚ, ɤɨɬɨɪɵɟ ɡɚɬɟɦ ɨɛɴɟɞɢɧɹɥɢɫɶ ɞɥɹ ɩɨɥɭɱɟɧɢɹ ɡɧɚɱɢɦɨɝɨ ɢɬɨɝɚ, ɜ ɧɚɲɟɦ ɫɥɭɱɚɟ – id ɛɟɥɤɚ, ɫɨɨɬɜɟɬɫɬɜɭɸɳɟɝɨ ɛɟɥɤɨɜɨɦɭ ɩɹɬɧɭ ɧɚ ɛɟɥɤɨɜɨɦ ɝɟɥɟ (ɪɢɫ. 2.4). ɇɨɦɟɪ ɩɹɬɧɚ ɦɨɠɟɬ ɛɵɬɶ ɢɫɩɨɥɶɡɨɜɚɧ ɞɥɹ ɫɜɹɡɢ id ɫ ɞɪɭɝɢɦɢ ɷɬɚɩɚɦɢ ɩɪɨɬɟɨɦɧɨɝɨ ɚɧɚɥɢɡɚ. ɇɚ ɪɢɫ. 2.5 ɩɪɟɞɫɬɚɜɥɟɧ ɩɪɢɦɟɪ ɡɚɩɢɫɢ ɨ ɜɵɪɟɡɚɧɢɢ ɛɟɥɤɨɜɨɝɨ ɩɹɬɧɚ. ɉɪɟɞɫɬɚɜɥɟɧɧɨɟ ɜɵɲɟ ɫɨɨɛɳɟɧɢɟ ɝɟɧɟɪɢɪɭɟɬɫɹ ɞɥɹ ɤɚɠɞɨɝɨ ɝɟɥɹ ɢ ɩɪɟɞɫɬɚɜɥɹɟɬ ɫɨɛɨɣ ɜɚɠɧɭɸ ɫɜɹɡɶ ɦɟɠɞɭ ɝɟɥɟɜɵɦ ɫɬɨɥɛɢɤɨɦ, ɧɚɩɪɚɜɥɹɟɦɵɦ ɜ ɪɨɛɨɬ ɩɟɪɟɜɚɪɢɜɚɧɢɹ ɛɟɥɤɚ, ɢ ɛɟɥɤɨɜɵɦ ɩɹɬɧɨɦ ɧɚ ɝɟɥɟ. Ʉɚɠɞɵɣ ɝɟɥɶ ɩɨɥɭɱɚɥ ɫɨɛɫɬɜɟɧɧɨɟ ɧɚɢɦɟɧɨɜɚɧɢɟ, ɚ ɩɪɢɜɟɞɟɧɧɵɣ ɩɪɢɦɟɪ ɫɨɨɬɜɟɬɫɬɜɭɟɬ 664 ɢɡɜɥɟɱɟɧɧɵɦ ɛɟɥɤɚɦ. Ɋɢɫ. 2.4. Ȼɟɥɤɨɜɵɣ ɝɟɥɶ – ɤɚɠɞɨɟ ɛɟɥɤɨɜɨɟ ɩɹɬɧɨ ɧɚ ɢɡɨɛɪɚɠɟɧɢɢ ɝɟɥɹ ɢɦɟɟɬ ɡɧɚɱɟɧɢɟ id 55 Ɋɢɫ. 2.5. ɋɨɨɛɳɟɧɢɟ (ɡɚɩɢɫɶ) ɨ ɜɵɪɟɡɚɧɢɢ ɛɟɥɤɨɜ – ɤɚɠɞɨɟ ɛɟɥɤɨɜɨɟ ɩɹɬɧɨ ɫɨɨɬɜɟɬɫɬɜɭɟɬ ɧɨɦɟɪɭ ɹɱɟɣɤɢ 2.17. ɂɞɟɧɬɢɮɢɤɚɰɢɹ ɛɟɥɤɨɜ ɇɚ ɪɢɫ. 2.6 ɩɪɟɞɫɬɚɜɥɟɧ ɩɪɢɦɟɪ ɡɚɩɢɫɢ (ɪɚɫɩɟɱɚɬɤɢ) ɢɞɟɧɬɢɮɢɰɢɪɨɜɚɧɧɵɯ ɛɟɥɤɨɜ. ɍɪɨɜɟɧɶ ɜɟɪɨɹɬɧɨɫɬɢ ɩɨɡɜɨɥɹɟɬ ɨɰɟɧɢɬɶ ɨɬɧɨɫɢɬɟɥɶɧɭɸ ɧɚɞɟɠɧɨɫɬɶ ɩɨɥɭɱɟɧɧɨɣ ɢɞɟɧɬɢɮɢɤɚɰɢɢ ɛɟɥɤɚ. Ⱦɚɥɟɟ ɛɟɥɨɤ ɦɨɠɟɬ ɚɧɚɥɢɡɢɪɨɜɚɬɶɫɹ ɫ ɩɨɦɨɳɶɸ ɛɚɡɵ ɞɚɧɧɵɯ SwissProt, ɤɨɬɨɪɚɹ ɩɨɡɜɨɥɹɟɬ ɭɬɨɱɧɢɬɶ ɧɟ ɬɨɥɶɤɨ ɟɝɨ ɮɭɧɤɰɢɢ, ɧɨ ɢ ɤɨɦɩɚɪɬɦɟɧɬɚɥɢɡɚɰɢɸ. ȼ ɤɨɧɟɱɧɨɦ ɫɱɟɬɟ, ɤɚɪɬɢɪɨɜɚɧɢɟ ɝɟɧɨɦɚ ɨɛɟɫɩɟɱɢɜɚɟɬ ɧɟɨɛɯɨɞɢɦɭɸ ɢɧɮɨɪɦɚɰɢɸ ɞɥɹ ɞɚɥɶɧɟɣɲɢɯ ɫɪɚɜɧɢɬɟɥɶɧɵɯ ɢɫɫɥɟɞɨɜɚɧɢɣ. 56 Ɋɢɫ. 2.6. ɉɪɢɦɟɪ ɢɞɟɧɬɢɮɢɤɚɰɢɢ ɛɟɥɤɨɜ – ɤɚɠɞɨɦɭ ɧɨɦɟɪɭ ɹɱɟɣɤɢ ɫɨɨɬɜɟɬɫɬɜɭɟɬ ɛɟɥɨɤ ɢ ɜɟɪɨɹɬɧɨɫɬɶ ɟɝɨ ɩɪɚɜɢɥɶɧɨɣ ɢɞɟɧɬɢɮɢɤɚɰɢɢ Ⱦɥɹ ɢɞɟɧɬɢɮɢɤɚɰɢɢ ɛɟɥɤɨɜ ɜ ɤɚɪɞɢɨɩɪɟɩɚɪɚɬɚɯ ɫɩɟɤɬɪɵ ɩɨɝɥɨɳɟɧɢɹ ɡɚɯɜɚɬɵɜɚɥɢ ɜ ɪɟɠɢɦɟ ɩɨɥɨɠɢɬɟɥɶɧɨ ɡɚɪɹɠɟɧɧɵɯ ɢɨɧɨɜ, ɢɫɩɨɥɶɡɭɹ 355-ɧɦ Nd:YAG ɥɚɡɟɪ ɫ ɱɚɫɬɨɬɨɣ 200 Ƚɰ, ɢ ɩɨɥɭɱɚɥɢ ɨɬ 100 ɞɨ 2000 ɢɧɞɢɜɢɞɭɚɥɶɧɵɯ ɫɩɟɤɬɪɨɜ. Ⱦɥɹ ɚɧɚɥɢɡɚ ɮɪɚɝɦɟɧɬɨɜ ɢɨɧɨɜ ɜ ɬɚɧɞɟɦɟ TOF/TOF, ɢɨɧɵ-ɩɪɟɞɲɟɫɬɜɟɧɧɢɤɢ ɭɫɤɨɪɹɥɢɫɶ ɞɨ 8 ɤȼ ɢ ɨɬɛɢɪɚɥɢɫɶ ɜ ɩɨɪɬɭ ɜɯɨɞɚ ɢɨɧɨɜ. Ɏɪɚɝɦɟɧɬɵ, ɜɨɡɧɢɤɚɸɳɢɟ ɜ ɪɟɡɭɥɶɬɚɬɟ ɫɬɨɥɤɧɨɜɟɧɢɹ ɦɟɠɞɭ ɩɪɟɞɲɟɫɬɜɟɧɧɢɤɚɦɢ ɢ ɜɨɡɞɭɯɨɦ ɜ ɤɨɥɥɢɡɢɨɧɧɨɣ ɤɚɦɟɪɟ, ɛɵɥɢ ɭɫɤɨɪɟɧɵ ɞɨ 15 ɤȼ ɜ ɢɫɬɨɱɧɢɤɟ 2, ɢ ɢɯ ɦɚɫɫɵ ɛɵɥɢ ɩɪɨɚɧɚɥɢɡɢɪɨɜɚɧɵ ɩɨɫɥɟ ɩɪɨɯɨɠɞɟɧɢɹ ɨɬɪɚɠɚɬɟɥɹ ɢɨɧɨɜ. Ⱦɚɧɧɵɟ ɨ ɦɚɫɫɚɯ ɛɵɥɢ ɩɪɨɚɧɚɥɢɡɢɪɨɜɚɧɵ ɚɜɬɨɦɚɬɢɱɟɫɤɢ ɫ ɩɨɦɨɳɶɸ ɩɪɨɝɪɚɦɦɧɨɝɨ ɩɚɤɟɬɚ 4000 Series Explorer ɜɟɪɫɢɢ 3.5.3 (Applied Biosystems). ȼɧɭɬɪɟɧɧɹɹ ɤɚɥɢɛɪɨɜɤɚ MALDI-TOF ɩɪɨɜɨɞɢɥɚɫɶ ɫ ɢɫɩɨɥɶɡɨɜɚɧɢɟɦ 2 ɢɨɧɨɜ ɚɜɬɨɥɢɡɚ ɬɪɢɩɫɢɧɚ (m/z=842,510 ɢ m/z=2211.105, ɫɨɨɬɜɟɬɫɬɜɟɧɧɨ). Ʉɚɥɢɛɪɨɜɤɚ MALDI-MS/MS ɩɪɨɜɨɞɢɥɚɫɶ ɫ ɢɫɩɨɥɶɡɨɜɚɧɢɟɦ ɢɨɧɧɵɯ ɫɩɟɤɬɪɨɜ ɮɪɚɝɦɟɧɬɨɜ Glu1-ɮɢɛɪɢɧɨɩɟɩɬɢɞɚ B (4800 MALDI/TOFTOF, Applied Biosystems). Ⱦɚɧɧɵɟ MALDI-MS ɢ MS/MS ɛɵɥɢ ɨɛɴɟ- 57 ɞɢɧɟɧɵ ɫ ɩɨɦɨɳɶɸ ɩɪɨɝɪɚɦɦɵ GPS Explorer ɜɟɪɫɢɢ 3.6, ɤɨɬɨɪɚɹ ɩɨɡɜɨɥɹɟɬ ɩɪɨɜɨɞɢɬɶ ɧɟɪɟɡɟɪɜɢɪɭɸɳɢɣ ɩɨɢɫɤ ɜ ɛɚɡɟ ɞɚɧɧɵɯ ɛɟɥɤɨɜ NCBI (ɜɟɪɫɢɹ 20080225) ɫ ɢɫɩɨɥɶɡɨɜɚɧɢɟɦ ɩɪɨɝɪɚɦɦɵ Mascot ɜɟɪɫɢɢ 2.1 (Matrix science), ɩɪɢ ɞɨɩɭɫɤɟ ɨɲɢɛɤɢ ɨɩɪɟɞɟɥɟɧɢɹ ɦɚɫɫɨɜɨɣ ɞɨɥɢ ɞɨ 50 ppm ɢ ɨɞɧɨɝɨ ɩɪɨɩɭɫɤɚ ɪɚɫɳɟɩɥɟɧɢɹ. 58 3. ɉɈɅɍɑȿɇɇɕȿ ɊȿɁɍɅɖɌȺɌɕ 3.1 ȼɥɢɹɧɢɟ ɩɚɪɚɬɢɪɟɨɢɞɧɨɝɨ ɝɨɪɦɨɧɚ ɧɚ ɨɫɬɟɨɛɥɚɫɬɵ ɂɡɜɟɫɬɧɨ, ɱɬɨ ɤɨɦɩɨɧɟɧɬɵ ɬɚɤ ɧɚɡɵɜɚɟɦɵɯ «ɧɢɲ» ɋɄ [108] ɨɩɪɟɞɟɥɹɸɬ ɢɯ ɮɭɧɤɰɢɨɧɚɥɶɧɨɟ ɫɨɫɬɨɹɧɢɟ ɢ, ɜ ɱɚɫɬɧɨɫɬɢ, ɩɪɟɩɹɬɫɬɜɭɸɬ ɩɨɬɟɪɟ ɜɵɫɨɤɨɝɨ ɩɪɨɥɢɮɟɪɚɬɢɜɧɨɝɨ ɩɨɬɟɧɰɢɚɥɚ. ɍɫɬɚɧɨɜɥɟɧɨ, ɱɬɨ ɜɚɠɧɵɦ ɫɬɪɭɤɬɭɪɧɵɦ ɷɥɟɦɟɧɬɨɦ ɧɢɲ ɹɜɥɹɸɬɫɹ ɨɫɬɟɨɛɥɚɫɬɵ, ɤɨɥɢɱɟɫɬɜɨ ɢ ɚɤɬɢɜɚɰɢɸ ɤɨɬɨɪɵɯ ɦɨɠɧɨ ɪɟɝɭɥɢɪɨɜɚɬɶ ɫ ɩɨɦɨɳɶɸ ɩɚɪɚɬɢɪɟɨɢɞɧɨɝɨ ɝɨɪɦɨɧɚ (ɉɌȽ). Ɉɫɬɟɨɛɥɚɫɬɵ ɫɬɢɦɭɥɢɪɭɸɬɫɹ ɉɌȽ ɢɥɢ ɥɨɤɚɥɶɧɨ ɨɛɪɚɡɭɸɳɢɦɫɹ ɫɜɹɡɚɧɧɵɦ ɫ ɧɢɦ ɛɟɥɤɨɦ (PTHrP) ɱɟɪɟɡ ɪɟɰɟɩɬɨɪ (PPR) ɤ ɧɢɦ [23, 24]. ȼ ɪɹɞɟ ɷɤɫɩɟɪɢɦɟɧɬɨɜ ɩɨɤɚɡɚɧɨ, ɱɬɨ ɩɨɫɥɟ ɢɧɴɟɤɰɢɣ ɧɟɛɨɥɶɲɢɯ ɤɨɥɢɱɟɫɬɜ ɉɌȽ, ɫɨɩɨɫɬɚɜɢɦɵɯ ɫ ɢɫɩɨɥɶɡɭɟɦɵɦɢ ɞɥɹ ɥɟɱɟɧɢɹ ɨɫɬɟɨɩɨɪɨɡɚ, ɱɢɫɥɨ ɫɚɦɵɯ ɪɚɧɧɢɯ ɩɨɥɢɩɨɬɟɧɬɧɵɯ ȽɋɄ ɭɜɟɥɢɱɢɜɚɟɬɫɹ ɜ 2 ɪɚɡɚ, ɚ ɦɵɲɢ, ɜɨɫɫɬɚɧɚɜɥɢɜɚɸɳɢɟɫɹ ɩɨɫɥɟ ɥɟɬɚɥɶɧɨɝɨ ɨɛɥɭɱɟɧɢɹ ɩɨɞ ɞɟɣɫɬɜɢɟɦ ɤɨɫɬɧɨɝɨ ɦɨɡɝɚ, ɨɛɪɚɛɨɬɚɧɧɨɝɨ ɉɌȽ, ɥɭɱɲɟ ɜɵɠɢɜɚɸɬ [26]. ɗɬɨɬ ɷɮɮɟɤɬ, ɜɢɞɢɦɨ, ɫɜɹɡɚɧ ɫ ɩɨɜɵɲɟɧɢɟɦ ɷɤɫɩɪɟɫɫɢɢ Jagged 1 – ɥɢɝɚɧɞɚ, ɥɨɤɚɥɢɡɨɜɚɧɧɨɝɨ ɧɚ ɩɨɜɟɪɯɧɨɫɬɢ ɨɫɬɟɨɛɥɚɫɬɨɜ, ɤɨɬɨɪɵɣ ɜɡɚɢɦɨɞɟɣɫɬɜɭɟɬ ɫ ɪɟɰɟɩɬɨɪɨɦ Notch 1, ɷɤɫɩɪɟɫɫɢɪɨɜɚɧɧɵɦ ɧɚ ɩɨɜɟɪɯɧɨɫɬɢ ȽɋɄ [49, 102]. Ɍɚɤɨɟ ɜɡɚɢɦɨɞɟɣɫɬɜɢɟ ɫɬɢɦɭɥɢɪɭɟɬ ɩɪɨɥɢɮɟɪɚɰɢɸ ȽɋɄ. ȼ ɬɨ ɠɟ ɜɪɟɦɹ ɦɨɥɟɤɭɥɹɪɧɵɟ ɦɟɯɚɧɢɡɦɵ ɜɡɚɢɦɨɞɟɣɫɬɜɢɹ ɉɌȽ ɢ ɨɫɬɟɨɛɥɚɫɬɨɜ ɨɫɬɚɸɬɫɹ ɦɚɥɨɢɡɭɱɟɧɧɵɦɢ, ɱɬɨ ɧɟ ɩɨɡɜɨɥɹɟɬ ɜ ɞɨɥɠɧɨɣ ɦɟɪɟ ɢɧɬɟɪɩɪɟɬɢɪɨɜɚɬɶ ɜɥɢɹɧɢɟ ɩɨɫɥɟɞɧɢɯ ɧɚ ȽɋɄ. ȼ ɷɬɨɣ ɫɜɹɡɢ ɰɟɥɶɸ ɩɟɪɜɨɣ ɱɚɫɬɢ ɧɚɲɟɝɨ ɢɫɫɥɟɞɨɜɚɧɢɹ ɹɜɢɥɨɫɶ ɜɵɹɜɥɟɧɢɟ ɛɟɥɤɨɜ ɨɫɬɟɨɛɥɚɫɬɨɜ, ɢɡɦɟɧɹɸɳɢɯɫɹ ɩɨɞ ɞɟɣɫɬɜɢɟɦ ɝɨɪɦɨɧɚ, ɹɜ- 59 ɥɹɸɳɟɝɨɫɹ, ɩɨ ɫɭɬɢ ɞɟɥɚ, ɡɚɩɭɫɤɚɸɳɢɦ ɡɜɟɧɨɦ ɜɡɚɢɦɨɞɟɣɫɬɜɢɹ ɦɟɠɞɭ ɨɫɬɟɨɛɥɚɫɬɚɦɢ ɤɚɤ ɤɨɦɩɨɧɟɧɬɚɦɢ ɧɢɲɢ, ɢ ɧɚɯɨɞɹɳɢɦɢɫɹ ɜ ɧɟɣ ȽɋɄ. ȼ ɷɤɫɩɟɪɢɦɟɧɬɚɯ ɢɫɩɨɥɶɡɨɜɚɧɚ ɤɥɟɬɨɱɧɚɹ ɥɢɧɢɹ ɨɫɬɟɨɛɥɚɫɬɩɨɞɨɛɧɨɣ ɨɫɬɟɨɫɚɪɤɨɦɵ MG63 ɱɟɥɨɜɟɤɚ ɜ ɤɚɱɟɫɬɜɟ ɦɨɞɟɥɢ ɞɥɹ ɢɫɫɥɟɞɨɜɚɧɢɹ ɷɮɮɟɤɬɨɜ ɉɌȽ (ɮɪɚɝɦɟɧɬ ɱɟɥɨɜɟɱɟɫɤɨɝɨ ɉɌȽ ɫ ɚɦɢɧɨɤɢɫɥɨɬɚɦɢ 1–34). Ʉɥɟɬɤɢ ɤɭɥɶɬɢɜɢɪɨɜɚɥɢ ɜ ɫɪɟɞɟ Dulbecco"s Modified Eagle (DɆȿɆ), ɫɨɞɟɪɠɚɳɟɣ 10% ɷɦɛɪɢɨɧɚɥɶɧɭɸ ɛɵɱɶɸ ɫɵɜɨɪɨɬɤɭ, 1% L-ɝɥɭɬɚɦɢɧ, 1% ɚɧɬɢɛɢɨɬɢɤ-ɚɧɬɢɦɢɤɨɬɢɤ ɢ 1% ɡɚɦɟɧɢɦɵɯ ɚɦɢɧɨɤɢɫɥɨɬ ɜ 5% ɋɈ2 ɢɧɤɭɛɚɬɨɪɟ ɩɪɢ ɬɟɦɩɟɪɚɬɭɪɟ 370ɋ. ɉɪɢ 70%-ɨɣ ɤɨɧɮɥɭɟɧɬɧɨɫɬɢ ɤɥɟɬɤɢ ɛɵɥɢ ɩɟɪɟɧɟɫɟɧɵ ɜ «ɨɛɟɞɧɟɧɧɭɸ» ɫɪɟɞɭ 0,1% ɎȻɋ (ɮɟɬɚɥɶɧɨɣ ɛɵɱɶɟɣ ɫɵɜɨɪɨɬɤɢ) ɧɚ 48 ɱɚɫɨɜ ɞɥɹ ɫɢɧɯɪɨɧɢɡɚɰɢɢ ɜ ɮɚɡɟ G1 ɩɟɪɟɞ ɞɨɛɚɜɥɟɧɢɟɦ 10–7 Ɇ ɉɌȽ ɢɥɢ ɤɨɧɬɪɨɥɶɧɨɝɨ ɫɨɥɟɜɨɝɨ ɪɚɫɬɜɨɪɚ. FACS ɢɫɩɨɥɶɡɨɜɚɥɫɹ ɞɥɹ ɩɨɞɬɜɟɪɠɞɟɧɢɹ G1 ɫɢɧɯɪɨɧɢɡɚɰɢɢ ɨɛɟɞɧɟɧɧɵɯ ɫɵɜɨɪɨɬɤɨɣ ɤɥɟɬɨɤ MG63. Ʉɥɟɬɤɢ, ɡɚɮɢɤɫɢɪɨɜɚɧɧɵɟ 70% ɷɬɚɧɨɥɨɦ, ɞɜɚɠɞɵ ɩɪɨɦɵɜɚɥɢ ɮɨɫɮɚɬ-ɰɢɬɪɚɬɧɵɦ ɛɭɮɟɪɧɵɦ ɪɚɫɬɜɨɪɨɦ ɢ ɪɟɫɭɫɩɟɧɞɢɪɨɜɚɥɢ ɜ 50 ɦɤɥ 100 ɦɤɝ/ɦɥ ɊɇɄɚɡɵ-Ⱥ ɢ 300 ɦɤɥ 50 ɦɤɝ/ɦɥ ɩɪɨɩɢɞɢɭɦ-ɢɨɞɢɞɚ ɢ ɢɧɤɭɛɢɪɨɜɚɥɢ ɩɪɢ ɤɨɦɧɚɬɧɨɣ ɬɟɦɩɟɪɚɬɭɪɟ ɜ ɬɟɱɟɧɢɟ 30 ɦɢɧ. Ɉɛɳɟɟ ɤɨɥɢɱɟɫɬɜɨ ɤɥɟɬɨɤ (10 000 ɧɚ ɩɨɩɭɥɹɰɢɸ) ɚɧɚɥɢɡɢɪɨɜɚɥɨɫɶ ɫ ɩɨɦɨɳɶɸ FACSvCalibur ɩɪɨɬɨɱɧɨɝɨ ɰɢɬɨɦɟɬɪɚ (Becton Dickenson) ɢ ɦɚɪɤɟɪɵ ɤɥɟɬɨɱɧɨɝɨ ɰɢɤɥɚ ɢɫɩɨɥɶɡɨɜɚɥɢɫɶ ɞɥɹ ɩɨɫɬɪɨɟɧɢɹ ɝɢɫɬɨɝɪɚɦɦ ɫɨɞɟɪɠɚɧɢɹ ȾɇɄ ɫ ɩɨɦɨɳɶɸ ɤɨɦɩɶɸɬɟɪɧɨɝɨ ɩɚɤɟɬɚ CellQuest Pro Software, ɩɨɡɜɨɥɹɸɳɟɝɨ ɨɰɟɧɢɜɚɬɶ ɩɪɨɩɨɪɰɢɢ ɤɥɟɬɨɤ ɜ G0/G1, S ɢ G2/M ɮɚɡɚɯ ɤɥɟɬɨɱɧɨɝɨ ɰɢɤɥɚ. FACS-ɚɧɚɥɢɡ ɢɫɩɨɥɶɡɨɜɚɥɫɹ ɬɚɤɠɟ ɞɥɹ ɨɩɪɟɞɟɥɟɧɢɹ, ɢɧɞɭɰɢɪɭɟɬ ɥɢ ɛɨɥɟɟ ɞɥɢɬɟɥɶɧɨɟ «ɝɨɥɨɞɚɧɢɟ» ɚɩɨɩɬɨɡ ɜ ɤɨɧɬɪɨɥɶɧɵɯ ɤɥɟɬɤɚɯ (ɱɟɪɟɡ 32 ɱɚɫɚ), ɢ ɫɬɢɦɭɥɢɪɭɟɬ ɥɢ ɨɛɪɚɛɨɬɤɚ ɉɌȽ ɝɨɥɨɞɚɸɳɢɯ MG63 ɤɥɟɬɤɢ (ɬɚɤɠɟ ɱɟɪɟɡ 32 ɱɚɫɚ) ɤ ɧɨɜɨɦɭ ɜɫɬɭɩɥɟɧɢɸ ɜ ɤɥɟɬɨɱɧɵɣ ɰɢɤɥ. 60 ȼ ɫɨɨɬɜɟɬɫɬɜɢɢ ɫ ɩɨɥɭɱɟɧɧɵɦɢ ɪɟɡɭɥɶɬɚɬɚɦɢ, 48-ɱɚɫɨɜɨɟ ɝɨɥɨɞɚɧɢɟ ɛɵɥɨ ɞɨɫɬɚɬɨɱɧɵɦ ɞɥɹ ɫɢɧɯɪɨɧɢɡɚɰɢɢ MG63 ɤɥɟɬɨɤ ɜ ɫɬɚɞɢɢ G0/G1 ɤɥɟɬɨɱɧɨɝɨ ɰɢɤɥɚ (ɩɪɢɛɥɢɡɢɬɟɥɶɧɨ 90% ɤɥɟɬɨɤ ɧɚɯɨɞɢɥɢɫɶ ɜ ɫɨɫɬɨɹɧɢɢ ɮɚɡɵ G0/G1). Ʉɚɤ ɩɨɤɚɡɚɧɨ ɫ ɩɨɦɨɳɶɸ FACS, ɞɨɩɨɥɧɢɬɟɥɶɧɵɟ 32 ɱɚɫɚ ɫɵɜɨɪɨɬɨɱɧɨɝɨ ɝɨɥɨɞɚɧɢɹ ɜ ɤɨɧɬɪɨɥɶɧɨɣ ɩɨɩɭɥɹɰɢɢ, ɨɛɪɚɛɨɬɚɧɧɨɣ ɫɨɥɟɜɵɦ ɪɚɫɬɜɨɪɨɦ, ɧɟ ɢɧɞɭɰɢɪɨɜɚɥɢ ɚɩɨɩɬɨɡ ɜ MG63 ɤɥɟɬɤɚɯ, ɚ ɤɥɟɬɤɢ, ɨɛɪɚɛɨɬɚɧɧɵɟ ɉɌȽ ɜ ɬɟɱɟɧɢɟ 32 ɱɚɫɨɜ, ɧɟ ɛɵɥɢ ɫɬɢɦɭɥɢɪɨɜɚɧɵ ɤ ɩɨɜɬɨɪɧɨɦɭ ɜɫɬɭɩɥɟɧɢɸ ɜ ɤɥɟɬɨɱɧɵɣ ɰɢɤɥ ɢɡ ɫɬɚɞɢɢ ɩɨɤɨɹ. ɉɪɢɦɟɪɧɨ 3×106 ɤɥɟɬɨɤ ɛɵɥɢ ɜɡɹɬɵ ɱɟɪɟɡ 4, 8, ɢ 32 ɱɚɫɚ ɩɨɫɥɟ ɜɡɚɢɦɨɞɟɣɫɬɜɢɹ ɫ ɉɌȽ ɢ ɢɡ ɤɨɧɬɪɨɥɹ ɢ ɯɪɚɧɢɥɢɫɶ ɩɪɢ –80°C. ɇɚɛɨɪ Clean-Up ɢɫɩɨɥɶɡɨɜɚɥɫɹ ɞɥɹ ɭɞɚɥɟɧɢɹ ɩɪɢɦɟɫɟɣ ɩɟɪɟɞ ɡɚɝɪɭɡɤɨɣ ɧɚ 2D ɜ ɩɟɪɜɨɦ ɧɚɩɪɚɜɥɟɧɢɢ. Ʉɨɧɰɟɧɬɪɚɰɢɹ ɛɟɥɤɚ ɤɨɥɢɱɟɫɬɜɟɧɧɨ ɨɩɪɟɞɟɥɹɥɚɫɶ ɫ ɩɨɦɨɳɶɸ ɧɚɛɨɪɚ ȼɋȺ. Ʌɢɡɚɬɵ (50 ɦɤɝ ɛɟɥɤɚ) ɧɚɧɨɫɢɥɢɫɶ ɧɚ ɨɛɟɡɜɨɠɟɧɧɵɟ IPG-ɫɬɪɢɩɵ ɫ ɩɨɦɨɳɶɸ ɩɪɢɛɨɪɚ IPGphor II (GE- Healthcare). Ɋɟɡɭɥɶɬɚɬɵ, ɯɚɪɚɤɬɟɪɢɡɭɸɳɢɟ ɢɞɟɧɬɢɮɢɤɚɰɢɸ ɛɟɥɤɨɜ ɢ ɢɯ ɩɨɜɟɞɟɧɢɟ ɤɚɤ ɫɥɟɞɫɬɜɢɟ ɜɡɚɢɦɨɞɟɣɫɬɜɢɹ ɫ ɉɌȽ ɜ ɬɟɱɟɧɢɟ 4, 8 ɢ 32 ɱɚɫɨɜ, ɩɪɟɞɫɬɚɜɥɟɧɵ ɜ ɬɚɛɥ. 3.1. ȼ ɫɨɜɨɤɭɩɧɨɫɬɢ ɫ ɞɚɧɧɵɦɢ ɩɨ ɨɤɪɚɲɢɜɚɧɢɸ ɤɥɟɬɨɤ, ɨɧɢ ɫɜɢɞɟɬɟɥɶɫɬɜɭɸɬ ɨ ɫɥɟɞɭɸɳɟɦ. ɉɌȽ ɫɬɢɦɭɥɢɪɭɟɬ ɜɵɠɢɜɚɧɢɟ ɧɚɯɨɞɹɳɢɯɫɹ ɜ ɫɬɚɞɢɢ ɩɨɤɨɹ (ɥɢɲɟɧɧɵɯ ɩɢɬɚɧɢɹ) ɨɫɬɟɨɛɥɚɫɬɨɜ. ɂɯ ɨɬɦɢɪɚɧɢɟ, ɚɫɫɨɰɢɢɪɨɜɚɧɧɨɟ ɫ ɮɚɤɬɨɪɨɦ ɬɪɚɧɫɤɪɢɩɰɢɢ 1, ɫɧɢɠɚɟɬɫɹ ɜ 4 ɪɚɡɚ ɩɨɫɥɟ ɨɛɪɚɛɨɬɤɢ ɉɌȽ ɩɨ ɫɪɚɜɧɟɧɢɸ ɫ ɤɨɧɬɪɨɥɟɦ. ȼɫɟɝɨ ɢɞɟɧɬɢɮɢɰɢɪɨɜɚɧɨ 15 ɛɟɥɤɨɜ, ɤɨɥɢɱɟɫɬɜɨ ɤɨɬɨɪɵɯ ɩɪɟɬɟɪɩɟɜɚɟɬ ɢɡɦɟɧɟɧɢɟ ɩɪɢ ɞɟɣɫɬɜɢɢ ɉɌȽ ɧɚ ɨɫɬɟɨɛɥɚɫɬɵ, ɩɪɢɱɟɦ ɤɚɠɞɨɟ ɭɞɥɢɧɟɧɢɟ ɜɪɟɦɟɧɢ ɜɥɢɹɧɢɹ ɉɌȽ ɧɚ ɨɫɬɟɨɛɥɚɫɬɵ ɩɪɢɜɨɞɢɬ ɤ ɨɛɧɚɪɭɠɟɧɢɸ ɧɨɜɵɯ ɛɟɥɤɨɜ, ɫɨɞɟɪɠɚɧɢɟ ɤɨɬɨɪɵɯ ɭɜɟɥɢɱɢɜɚɟɬɫɹ ɢɥɢ ɭɦɟɧɶɲɚɟɬɫɹ ɩɨ ɫɪɚɜɧɟɧɢɸ ɫ ɤɨɧɬɪɨɥɟɦ. 61 ɗɬɢ ɞɚɧɧɵɟ ɞɨɩɨɥɧɹɸɬ ɪɚɧɟɟ ɨɩɭɛɥɢɤɨɜɚɧɧɵɟ ɫɜɟɞɟɧɢɹ ɩɨ ɢɫɫɥɟɞɨɜɚɧɢɸ ɩɪɨɬɟɨɦɚ ɨɫɬɟɨɛɥɚɫɬɨɜ ɢɡ ɤɨɫɬɧɨɝɨ ɦɨɡɝɚ ɦɵɲɟɣ [4, 49]. Ɍɚɛɥɢɰɚ 3.1. ɂɞɟɧɬɢɮɢɰɢɪɨɜɚɧɧɵɟ ɫ ɩɨɦɨɳɶɸ ɩɪɨɬɟɨɦɢɤɢ ɛɟɥɤɢ ɨɫɬɟɨɛɥɚɫɬɨɜ, ɤɨɥɢɱɟɫɬɜɨ ɤɨɬɨɪɵɯ ɢɡɦɟɧɹɟɬɫɹ ɩɨɫɥɟ ɜɡɚɢɦɨɞɟɣɫɬɜɢɹ ɤɥɟɬɨɤ ɫ ɉɌȽ ɜ ɬɟɱɟɧɢɟ ɪɚɡɧɵɯ ɩɟɪɢɨɞɨɜ ɜɪɟɦɟɧɢ ɉɪɨɞɨɥɠɢɂɞɟɧɬɢɮɢɰɢɪɨɜɚɧɧɵɟ ɂɡɦɟɧɟɧɢɟ ɬɟɥɶɧɨɫɬɶ ɜɡɚɢɛɟɥɤɢ ɤɨɥɢɱɟɫɬɜɚ ɛɟɥɤɚ ɦɨɞɟɣɫɬɜɢɹ (ɱɚɫ) Ribosomal protein S6 kinase 3-ɤɪɚɬɧɨɟ ɫɧɢɠɟɧɢɟ Microtubule-associated pro2-ɤɪɚɬɧɨɟ ɭɜɟɥɢɱɟɧɢɟ tein tau 4 Putative NFkB activating 4-ɤɪɚɬɧɨɟ ɫɧɢɠɟɧɢɟ protein Endoplasmic-reticulum20-ɤɪɚɬɧɨɟ ɫɧɢɠɟɧɢɟ lumenal protein 28 Ran-specific GTPase9-ɤɪɚɬɧɨɟ ɭɜɟɥɢɱɟɧɢɟ activating protein Fibroblast growth factor-20 5-ɤɪɚɬɧɨɟ ɭɜɟɥɢɱɟɧɢɟ 8 Death receptor 5 4-ɤɪɚɬɧɨɟ ɫɧɢɠɟɧɢɟ Putative espin 3-ɤɪɚɬɧɨɟ ɭɜɟɥɢɱɟɧɢɟ Novel protein (MGC26989) 2- ɤɪɚɬɧɨɟ ɭɜɟɥɢɱɟɧɢɟ Fibrinogen-like protein expressed in T lymphocytes 2- ɤɪɚɬɧɨɟ ɫɧɢɠɟɧɢɟ (pT49) Ras guanine nucleotide ex10-ɤɪɚɬɧɨɟ ɫɧɢɠɟɧɢɟ change factor 2 Death associated transcrip4- ɤɪɚɬɧɨɟ ɫɧɢɠɟɧɢɟ tion factor 1 32 Microtubule-associated pro34-ɤɪɚɬɧɨɟ ɫɧɢɠɟɧɢɟ tein tau Hypothetical protein 3- ɤɪɚɬɧɨɟ ɫɧɢɠɟɧɢɟ FLJ43213 Hypothetical protein 5- ɤɪɚɬɧɨɟ ɫɧɢɠɟɧɢɟ FLJ31897 62 Ɍɚɤɢɦ ɨɛɪɚɡɨɦ, ɩɪɨɞɟɦɨɧɫɬɪɢɪɨɜɚɧɨ, ɱɬɨ ɢɫɩɨɥɶɡɭɟɦɚɹ ɦɟɬɨɞɢɤɚ ɩɪɨɬɟɨɦɧɨɝɨ ɚɧɚɥɢɡɚ ɹɜɥɹɟɬɫɹ ɷɮɮɟɤɬɢɜɧɵɦ ɢɧɫɬɪɭɦɟɧɬɨɦ ɞɥɹ ɦɨɧɢɬɨɪɢɧɝɚ ɢɡɦɟɧɟɧɢɣ ɛɟɥɤɨɜ ɜɚɠɧɟɣɲɢɯ ɤɥɟɬɨɤ «ɧɢɲɢ» ȽɋɄ ɜ ɨɬɜɟɬ ɧɚ ɝɨɪɦɨɧɚɥɶɧɭɸ ɫɬɢɦɭɥɹɰɢɸ. 3.2 Ⱥɧɚɥɢɡ ɩɪɨɬɟɨɦɚ ɝɟɦɨɩɨɷɬɢɱɟɫɤɢɯ ɫɬɜɨɥɨɜɵɯ ɤɥɟɬɨɤ 3.2.1 Ɇɨɧɨɧɭɤɥɟɚɪɧɵɟ ɤɥɟɬɤɢ ɉɨɩɭɥɹɰɢɹ ɦɨɧɨɧɭɤɥɟɚɪɧɵɯ ɤɥɟɬɨɤ (ɆɇɄ) ɛɵɥɚ ɜɵɞɟɥɟɧɚ ɢɡ ɨɞɧɨɝɨ ɨɛɪɚɡɰɚ ɩɭɩɨɜɢɧɧɨɣ ɤɪɨɜɢ (ɉɄ). Ɋɚɡɞɟɥɟɧɢɟ ɟɝɨ ɧɚ ɞɜɟ ɱɚɫɬɢ ɩɪɢɜɟɥɨ ɤ ɨɛɪɚɡɨɜɚɧɢɸ ɨɛɪɚɡɰɨɜ (Ⱥ ɢ Ȼ) ɩɨ ɨɞɧɨɦɭ ɦɢɥɥɢɨɧɭ ɆɇɄ, ɤɨɬɨɪɵɟ ɡɚɬɟɦ ɛɵɥɢ ɩɨɞɜɟɪɝɧɭɬɵ ɩɪɨɬɟɨɦɧɨɦɭ ɚɧɚɥɢɡɭ ɤɚɤ ɨɩɢɫɚɧɨ ɜ ɪɚɡɞɟɥɟ «Ɇɟɬɨɞɵ». Ⱦɜɟ ɚɥɢɤɜɨɬɵ Ⱥ ɢ Ȼ ɛɵɥɢ ɢɫɫɥɟɞɨɜɚɧɵ ɩɚɪɚɥɥɟɥɶɧɨ, ɱɬɨ ɩɪɢɜɟɥɨ ɤ ɩɨɥɭɱɟɧɢɸ ɜɡɚɢɦɨɫɜɹɡɚɧɧɵɯ ɩɪɨɬɟɨɦɧɵɯ ɩɪɨɮɢɥɟɣ ɩɨɩɭɥɹɰɢɢ ɆɇɄ. Ɋɚɡɞɟɥɟɧɢɟ ɜ ɝɟɥɟ ɜɫɟɯ ɱɟɬɵɪɟɯ ɮɪɚɤɰɢɣ, ɩɨɥɭɱɟɧɧɵɯ ɩɨɫɥɟ ɥɢɡɢɫɚ ɜɧɟɲɧɟɣ ɦɟɦɛɪɚɧɵ ɆɇɄ (ɫɦ. ɪɚɡɞɟɥ «Ɇɟɬɨɞɵ») – Ⱥ ɢ Ȼ ɜ ɞɜɨɣɧɨɣ ɩɨɜɬɨɪɧɨɫɬɢ – ɩɨɤɚɡɚɧɨ ɧɚ ɢɡɨɛɪɚɠɟɧɢɹɯ ɝɟɥɟɣ ɧɢɠɟ (ɪɢɫ. 3.1–3.4). Ⱥ Ȼ Ɋɢɫ. 3.1. ɉɪɨɬɟɨɦɧɵɟ ɩɪɨɮɢɥɢ ɩɪɢ ɪɚɡɞɟɥɟɧɢɢ ɜ ɝɟɥɟ ɩɟɪɜɨɣ ɮɪɚɤɰɢɢ ɆɇɄ ɢɡ ɨɞɧɨɣ ɚɥɢɤɜɨɬɵ ɜ ɞɜɨɣɧɨɣ ɩɨɜɬɨɪɧɨɫɬɢ (Ⱥ ɢ Ȼ). 63 Ⱥ Ȼ Ɋɢɫ. 3.2. ɉɪɨɬɟɨɦɧɵɟ ɩɪɨɮɢɥɢ ɩɪɢ ɪɚɡɞɟɥɟɧɢɢ ɜ ɝɟɥɟ ɜɬɨɪɨɣ ɮɪɚɤɰɢɢ ɆɇɄ ɢɡ ɨɞɧɨɣ ɚɥɢɤɜɨɬɵ ɜ ɞɜɨɣɧɨɣ ɩɨɜɬɨɪɧɨɫɬɢ (Ⱥ ɢ Ȼ). Ⱥ Ȼ Ɋɢɫ. 3.3. ɉɪɨɬɟɨɦɧɵɟ ɩɪɨɮɢɥɢ ɩɪɢ ɪɚɡɞɟɥɟɧɢɢ ɜ ɝɟɥɟ ɬɪɟɬɶɟɣ ɮɪɚɤɰɢɢ ɆɇɄ ɢɡ ɨɞɧɨɣ ɚɥɢɤɜɨɬɵ ɜ ɞɜɨɣɧɨɣ ɩɨɜɬɨɪɧɨɫɬɢ (Ⱥ ɢ Ȼ). Ⱥ Ȼ Ɋɢɫ. 3.4. ɉɪɨɬɟɨɦɧɵɟ ɩɪɨɮɢɥɢ ɩɪɢ ɪɚɡɞɟɥɟɧɢɢ ɜ ɝɟɥɟ ɱɟɬɜɟɪɬɨɣ ɮɪɚɤɰɢɢ ɆɇɄ ɢɡ ɨɞɧɨɣ ɚɥɢɤɜɨɬɵ ɜ ɞɜɨɣɧɨɣ ɩɨɜɬɨɪɧɨɫɬɢ (Ⱥ ɢ Ȼ). 64 ɉɪɟɞɫɬɚɜɥɟɧɧɵɟ ɜɵɲɟ ɢɡɨɛɪɚɠɟɧɢɹ ɯɚɪɚɤɬɟɪɢɡɭɸɬ ɩɪɨɬɟɨɦɧɵɣ ɩɪɨɮɢɥɶ ɩɨɩɭɥɹɰɢɢ ɦɨɧɨɧɭɤɥɟɚɪɧɵɯ ɝɟɦɨɩɨɷɬɢɱɟɫɤɢɯ ɫɬɜɨɥɨɜɵɯ ɤɥɟɬɨɤ (ɆɇɄ). Ɍɨɬ ɮɚɤɬ, ɱɬɨ ɤɥɟɬɤɢ ɛɵɥɢ ɜɵɞɟɥɟɧɵ ɢɡ ɨɞɧɨɝɨ ɨɛɪɚɡɰɚ, ɨɡɧɚɱɚɟɬ, ɱɬɨ ɩɨɩɭɥɹɰɢɹ ɤɥɟɬɨɤ ɫɨɨɬɜɟɬɫɬɜɭɟɬ ɨɞɧɨɦɭ ɢɧɞɢɜɢɞɭɭɦɭ (ɞɨɧɨɪɭ). Ɋɚɡɞɟɥɟɧɢɟ ɨɛɪɚɡɰɚ ɧɚ ɞɜɟ ɱɚɫɬɢ ɩɨɡɜɨɥɢɥɨ ɩɨɥɭɱɢɬɶ ɞɜɟ ɩɨɪɰɢɢ ɩɨ 106 ɤɥɟɬɨɤ ɞɥɹ ɩɪɨɬɟɨɦɧɵɯ ɢɫɫɥɟɞɨɜɚɧɢɣ. ɉɪɢ ɷɬɨɦ ɩɪɟɫɥɟɞɨɜɚɥɢɫɶ ɞɜɟ ɰɟɥɢ: 1) ɨɩɪɟɞɟɥɢɬɶ ɩɪɨɬɟɨɦɧɵɣ ɩɪɨɮɢɥɶ ɆɇɄ; 2) ɭɫɬɚɧɨɜɢɬɶ ɜɨɡɦɨɠɧɭɸ ɜɚɪɢɚɛɟɥɶɧɨɫɬɶ ɞɚɧɧɵɯ ɩɨ ɞɜɭɦ ɩɪɨɛɚɦ. ɂɡɨɛɪɚɠɟɧɢɹ ɝɟɥɟɣ ɨɬɪɚɠɚɸɬ ɫɯɨɞɫɬɜɨ ɩɨɥɭɱɟɧɧɵɯ ɩɪɨɬɟɨɦɧɵɯ ɩɪɨɮɢɥɟɣ ɢ ɭɤɚɡɵɜɚɸɬ ɧɚ ɬɨ, ɱɬɨ ɚɥɢɤɜɨɬɵ, ɢɫɫɥɟɞɭɟɦɵɟ ɩɚɪɚɥɥɟɥɶɧɨ ɢ ɨɞɧɨɜɪɟɦɟɧɧɨ, ɩɪɢɜɨɞɹɬ ɤ ɩɨɥɭɱɟɧɢɸ ɩɪɚɤɬɢɱɟɫɤɢ ɨɞɢɧɚɤɨɜɵɯ ɪɟɡɭɥɶɬɚɬɨɜ. Ⱦɥɹ ɭɝɥɭɛɥɟɧɧɨɣ ɨɰɟɧɤɢ ɪɚɡɥɢɱɢɣ ɦɟɠɞɭ ɨɞɢɧɚɤɨɜɵɦɢ ɨɛɪɚɡɰɚɦɢ, ɢɫɫɥɟɞɭɟɦɵɦɢ ɩɚɪɚɥɥɟɥɶɧɨ, ɢɡɨɛɪɚɠɟɧɢɹ ɛɵɥɢ ɩɨɞɜɟɪɝɧɭɬɵ ɞɨɩɨɥɧɢɬɟɥɶɧɨɦɭ ɚɧɚɥɢɡɭ ɫ ɩɨɦɨɳɶɸ ɫɩɟɰɢɚɥɶɧɨɝɨ ɩɚɤɟɬɚ ɩɪɨɝɪɚɦɦ Phoretix Evolution (Nonlinear Dynamics) ɢ ɫɨɡɞɚɧɢɹ ɨɛɨɛɳɟɧɧɨɝɨ (ɦɨɧɬɚɠɧɨɝɨ) ɢɡɨɛɪɚɠɟɧɢɹ – ɛɟɥɤɨɜɨɣ ɤɚɪɬɵ. ɗɬɨ ɛɵɥɨ ɫɞɟɥɚɧɨ ɞɥɹ ɢɞɟɧɬɢɮɢɤɚɰɢɢ ɢɡɦɟɧɟɧɢɣ, ɜɨɡɧɢɤɚɸɳɢɯ ɬɨɥɶɤɨ ɜɫɥɟɞɫɬɜɢɟ ɷɤɫɩɟɪɢɦɟɧɬɚɥɶɧɵɯ ɭɫɥɨɜɢɣ, ɢ ɞɥɹ ɨɩɪɟɞɟɥɟɧɢɹ ɨɠɢɞɚɟɦɨɣ ɜɚɪɢɚɰɢɢ ɞɚɧɧɵɯ, ɧɟ ɡɚɜɢɫɹɳɟɣ ɨɬ ɪɟɝɭɥɢɪɭɸɳɟɝɨ ɜɥɢɹɧɢɹ ɨɤɪɭɠɟɧɢɹ ɧɚ ɛɟɥɤɢ ɆɇɄ. Ɏɪɚɤɰɢɨɧɢɪɭɹ ɨɛɪɚɡɰɵ ɜ ɱɟɬɵɪɟ ɪɚɡɧɵɟ ɮɪɚɤɰɢɢ, ɦɨɠɧɨ ɛɵɥɨ ɢɡɭɱɢɬɶ ɤɚɠɞɭɸ ɮɪɚɤɰɢɸ ɛɨɥɟɟ ɬɳɚɬɟɥɶɧɨ ɢ ɨɩɪɟɞɟɥɢɬɶ ɫ ɛɨɥɶɲɟɣ ɭɜɟɪɟɧɧɨɫɬɶɸ ɜɟɪɨɹɬɧɨɫɬɶ ɨɲɢɛɤɢ ɞɥɹ ɢɫɯɨɞɧɨɝɨ ɨɛɪɚɡɰɚ ɜ ɰɟɥɨɦ. ɉɨɫɬɪɨɟɧɢɟ ɦɨɧɬɚɠɧɨɝɨ ɢɡɨɛɪɚɠɟɧɢɹ ɨɫɭɳɟɫɬɜɥɹɥɨɫɶ ɜ ɜɢɞɟ ɧɟɫɤɨɥɶɤɢɯ ɩɨɫɥɟɞɨɜɚɬɟɥɶɧɵɯ ɷɬɚɩɨɜ. ɋɧɚɱɚɥɚ ɜɵɩɨɥɧɹɥɫɹ ɩɪɨɝɪɚɦɦɧɵɣ ɚɧɚɥɢɡ ɢɡɨɛɪɚɠɟɧɢɣ ɫ ɰɟɥɶɸ ɚɜɬɨɦɚɬɢɱɟɫɤɨɝɨ ɜɵɹɜɥɟɧɢɹ ɨɤɪɚ65 ɲɟɧɧɵɯ ɩɹɬɟɧ ɢ ɭɫɬɚɧɨɜɥɟɧɢɹ ɢɯ ɨɱɟɪɬɚɧɢɣ. Ɉɤɪɚɲɟɧɧɚɹ ɩɥɨɳɚɞɶ ɤɚɠɞɨɝɨ ɩɹɬɧɚ ɭɫɬɚɧɚɜɥɢɜɚɥɚɫɶ ɩɪɨɝɪɚɦɦɨɣ ɩɨ ɪɟɡɭɥɶɬɚɬɚɦ ɨɩɪɟɞɟɥɟɧɢɹ ɪɚɡɥɢɱɢɣ ɦɟɠɞɭ «ɬɟɦɧɵɦɢ» ɢ «ɫɜɟɬɥɵɦɢ» ɩɢɤɫɟɥɹɦɢ. ɉɨɫɤɨɥɶɤɭ ɩɹɬɧɚ ɢɦɟɸɬ ɪɚɡɧɭɸ ɫɬɟɩɟɧɶ ɨɤɪɚɫɤɢ ɢ ɦɨɝɭɬ ɫɥɢɜɚɬɶɫɹ ɫ ɮɨɧɨɦ, ɜ ɩɪɨɝɪɚɦɦɟ ɡɚɞɚɸɬɫɹ ɬɪɢ ɫɩɟɰɢɚɥɶɧɵɯ ɩɚɪɚɦɟɬɪɚ ɞɥɹ ɜɵɹɜɥɟɧɢɹ ɛɟɥɤɨɜɵɯ ɮɪɚɤɰɢɣ (ɩɹɬɟɧ, «spots»). Ɉɞɢɧ ɢɡ ɧɢɯ – ɩɚɪɚɦɟɬɪ «ɋɝɥɚɠɢɜɚɧɢɟ» («Smooth») ɫ ɩɨɦɨɳɶɸ ɚɥɝɨɪɢɬɦɚ ɞɢɮɮɭɡɧɨɝɨ ɫɝɥɚɠɢɜɚɧɢɹ ɨɛɟɫɩɟɱɢɜɚɟɬ ɢɞɟɧɬɢɮɢɤɚɰɢɸ ɧɚɢɛɨɥɟɟ ɫɢɥɶɧɨ ɜɵɪɚɠɟɧɧɵɯ ɩɹɬɟɧ, ɚ ɬɚɤɠɟ ɱɟɬɤɨɫɬɶ ɨɩɪɟɞɟɥɟɧɢɹ ɤɪɚɹ ɩɹɬɧɚ. Ⱦɥɹ ɬɨɝɨ, ɱɬɨɛɵ ɨɬɞɟɥɢɬɶ ɫɥɚɛɨ ɨɤɪɚɲɟɧɧɵɟ ɩɹɬɧɚ ɨɬ ɮɨɧɚ ɢ ɲɭɦɚ, ɢɡɦɟɧɹɟɬɫɹ ɩɚɪɚɦɟɬɪ «ȼɵɞɟɥɟɧɢɟ» («Saliency»). Ɍɪɟɬɢɣ ɩɚɪɚɦɟɬɪ «Ɇɢɧɢɦɚɥɶɧɚɹ ɩɥɨɳɚɞɶ» («Min Area») ɡɚɞɚɟɬ ɦɢɧɢɦɚɥɶɧɭɸ ɩɥɨɳɚɞɶ ɩɹɬɧɚ ɢ ɜɫɟ ɩɹɬɧɚ, ɨɛɥɚɞɚɸɳɢɟ ɩɥɨɳɚɞɶɸ ɧɢɠɟ ɷɬɨɝɨ ɡɧɚɱɟɧɢɹ, ɧɟ ɛɭɞɭɬ ɜɵɹɜɥɟɧɵ. Ⱦɚɥɟɟ ɧɚ ɜɬɨɪɨɦ ɷɬɚɩɟ ɨɛɪɚɛɨɬɤɢ ɢɡɨɛɪɚɠɟɧɢɣ ɨɫɭɳɟɫɬɜɥɹɟɬɫɹ ɫɛɨɪ ɫɜɟɞɟɧɢɣ ɨ ɩɹɬɧɚɯ ɢ ɩɨɫɬɪɨɟɧɢɟ ɬɪɟɯɦɟɪɧɵɯ ɦɨɞɟɥɟɣ ɧɚ ɢɯ ɨɫɧɨɜɟ. Ⱥɧɚɥɢɡ ɩɹɬɟɧ ɢɞɟɬ ɩɨ ɬɪɟɦ ɨɫɧɨɜɧɵɦ ɩɚɪɚɦɟɬɪɚɦ: «ɢɧɬɟɧɫɢɜɧɨɫɬɶ», «ɩɥɨɳɚɞɶ» ɢ «ɨɛɴɟɦ ɩɹɬɧɚ». «ɂɧɬɟɧɫɢɜɧɨɫɬɶ» – ɩɨɤɚɡɵɜɚɟɬ ɫɬɟɩɟɧɶ ɨɤɪɚɲɢɜɚɧɢɹ ɩɹɬɧɚ ɩɨ ɫɪɚɜɧɟɧɢɸ ɫ ɮɨɧɨɦ; ɩɪɢ ɷɬɨɦ ɛɟɪɟɬɫɹ ɡɧɚɱɟɧɢɟ ɧɚɢɛɨɥɟɟ ɫɢɥɶɧɨ ɨɤɪɚɲɟɧɧɵɯ ɩɢɤɫɟɥɟɣ ɫɚɦɨɝɨ ɩɹɬɧɚ ɢ ɧɚɢɛɨɥɟɟ ɫɜɟɬɥɨɣ ɨɛɥɚɫɬɢ ɛɥɢɠɚɣɲɟɝɨ ɮɨɧɚ, ɨɤɪɭɠɚɸɳɟɝɨ ɩɹɬɧɨ. «ɉɥɨɳɚɞɶ ɩɹɬɧɚ» – ɞɚɧɧɵɣ ɩɚɪɚɦɟɬɪ ɜɵɫɱɢɬɵɜɚɟɬ ɩɨ ɫɪɟɞɧɟɦɭ ɡɧɚɱɟɧɢɸ ɢɧɬɟɧɫɢɜɧɨɫɬɢ ɨɤɪɚɲɢɜɚɧɢɹ. «Ɉɛɴɟɦ ɩɹɬɧɚ» – ɜɵɱɢɫɥɹɟɬɫɹ ɢɡ ɩɨɤɚɡɚɬɟɥɹ ɩɥɨɳɚɞɶ ɩɹɬɧɚ, ɪɚɫɫɱɢɬɵɜɚɟɦɨɝɨ ɫɬɪɨɝɨ ɩɨ ɥɢɧɢɢ ɨɛɜɨɞɤɢ ɩɹɬɧɚ. ɂɬɨɝɨɜɵɟ ɬɪɟɯɦɟɪɧɵɟ ɦɨɞɟɥɢ ɩɪɟɞɫɬɚɜɥɹɸɬ ɫɨɛɨɣ ɧɚɛɨɪɵ ɩɢɤɨɜ; ɩɪɢ ɷɬɨɦ, ɱɟɦ ɛɨɥɶɲɟ ɢɧɬɟɧɫɢɜɧɨɫɬɶ, ɬɟɦ ɜɵɲɟ ɩɢɤ, ɢ ɬɟɦ ɛɨɥɶɲɟ ɤɨɧɰɟɧɬɪɚɰɢɹ ɛɟɥɤɚ ɜ ɞɚɧɧɨɣ ɮɪɚɤɰɢɢ. 66 ȼɚɠɧɵɦ ɞɨɫɬɨɢɧɫɬɜɨɦ ɩɪɨɝɪɚɦɦɵ Phoretix Evolution ɹɜɥɹɟɬɫɹ ɬɨ, ɱɬɨ ɨɧɚ ɩɨɡɜɨɥɹɟɬ ɩɪɨɜɨɞɢɬɶ ɫɪɚɜɧɢɬɟɥɶɧɵɣ ɚɧɚɥɢɡ ɧɟɫɤɨɥɶɤɢɯ ɢɡɨɛɪɚɠɟɧɢɣ ɞɜɭɦɟɪɧɵɯ ɷɥɟɤɬɪɨɮɨɪɟɝɪɚɦɦ (Ⱦɗ). ɉɪɢ ɪɟɲɟɧɢɢ ɩɨɞɨɛɧɵɯ ɡɚɞɚɱ ɨɛɳɢɟ ɩɹɬɧɚ, ɯɚɪɚɤɬɟɪɧɵɟ ɞɥɹ 2-ɯ ɢ ɛɨɥɟɟ Ⱦɗ, ɜɵɞɟɥɹɸɬɫɹ ɨɞɧɢɦ ɰɜɟɬɨɦ. Ⱦɚɥɟɟ ɞɥɹ ɧɢɯ ɦɨɠɧɨ ɡɚɞɚɬɶ ɫɪɟɞɧɟɚɪɢɮɦɟɬɢɱɟɫɤɢɟ ɯɚɪɚɤɬɟɪɢɫɬɢɤɢ, ɚ ɬɚɤɠɟ ɪɚɫɫɱɢɬɚɬɶ ɜɚɪɢɚɛɟɥɶɧɨɫɬɶ ɷɬɢɯ ɩɹɬɟɧ ɢ ɩɨɥɭɱɢɬɶ ɢɧɵɟ ɞɚɧɧɵɟ. ȿɫɥɢ ɩɪɢ ɚɧɚɥɢɡɟ ɫɪɚɜɧɢɜɚɟɦɵɯ ɢɡɨɛɪɚɠɟɧɢɣ ɜɵɹɜɥɹɸɬɫɹ ɩɹɬɧɚ, ɩɪɢɫɭɬɫɬɜɭɸɳɢɟ ɧɚ ɨɞɧɨɦ ɢɡɨɛɪɚɠɟɧɢɢ ɢ ɨɬɫɭɬɫɬɜɭɸɳɢɟ ɧɚ ɞɪɭɝɨɦ, ɥɢɛɨ ɨɬɥɢɱɚɸɳɢɟɫɹ ɤɨɥɢɱɟɫɬɜɟɧɧɨ ɢ ɤɚɱɟɫɬɜɟɧɧɨ ɜ ɡɧɚɱɢɬɟɥɶɧɨɣ ɫɬɟɩɟɧɢ, ɬɨ ɨɧɢ ɜɵɞɟɥɹɸɬɫɹ ɞɪɭɝɢɦ ɰɜɟɬɨɦ. Ɍɚɤɢɦ ɨɛɪɚɡɨɦ, ɩɨɹɜɥɹɟɬɫɹ ɨɱɟɧɶ ɭɞɨɛɧɵɣ ɢɧɫɬɪɭɦɟɧɬ ɞɚɠɟ ɞɥɹ ɜɢɡɭɚɥɶɧɨɝɨ ɚɧɚɥɢɡɚ Ⱦɗ, ɨɫɨɛɟɧɧɨ ɩɪɢ ɛɨɥɶɲɨɦ ɤɨɥɢɱɟɫɬɜɟ ɝɟɥɟɣ. ȼ ɩɪɨɰɟɫɫɟ ɬɚɤɨɝɨ ɚɧɚɥɢɡɚ ɜɫɟɦ ɨɛɧɚɪɭɠɟɧɧɵɦ ɩɹɬɧɚɦ ɚɜɬɨɦɚɬɢɱɟɫɤɢ ɩɪɢɫɜɚɢɜɚɟɬɫɹ ɭɧɢɤɚɥɶɧɵɣ ɧɨɦɟɪ, ɚ ɬɚɤɠɟ ɪɚɫɫɱɢɬɵɜɚɸɬɫɹ ɜɟɥɢɱɢɧɵ ɢɧɬɟɧɫɢɜɧɨɫɬɢ ɩɥɨɳɚɞɢ, ɨɛɴɟɦɚ ɢ ɢɯ ɩɪɨɰɟɧɬɧɵɯ ɫɨɨɬɧɨɲɟɧɢɣ. ȼɫɟ ɷɬɢ ɯɚɪɚɤɬɟɪɢɫɬɢɤɢ ɨɬɨɛɪɚɠɚɸɬɫɹ ɜ ɜɢɞɟ ɨɬɱɟɬɚ, ɤɨɬɨɪɵɣ ɡɚɬɟɦ ɦɨɠɧɨ ɷɤɫɩɨɪɬɢɪɨɜɚɬɶ ɜ ɪɚɡɥɢɱɧɵɟ ɩɪɢɥɨɠɟɧɢɹ. ɉɨɫɤɨɥɶɤɭ ɢɫɫɥɟɞɨɜɚɬɟɥɟɣ ɨɛɵɱɧɨ ɢɧɬɟɪɟɫɭɟɬ ɨɛɴɟɦ ɩɹɬɧɚ, ɤɨɬɨɪɵɣ ɜɵɱɢɫɥɹɟɬɫɹ ɫɬɪɨɝɨ ɩɨ ɥɢɧɢɢ ɨɛɜɨɞɤɢ ɩɹɬɧɚ, ɫɨɨɬɜɟɬɫɬɜɭɸɳɢɟ ɞɚɧɧɵɟ ɞɥɹ ɫɪɚɜɧɟɧɢɹ ɩɹɬɟɧ ɦɨɝɭɬ ɛɵɬɶ ɩɨɥɭɱɟɧɵ ɢɡ ɤɨɥɨɧɤɢ «Volume». Ⱦɥɹ ɬɨɝɨ, ɱɬɨɛɵ ɬɨɱɧɨ ɨɩɪɟɞɟɥɢɬɶ ɫɨɨɬɜɟɬɫɬɜɢɟ ɯɚɪɚɤɬɟɪɢɫɬɢɤ ɜ ɤɨɦɩɶɸɬɟɪɧɨɦ ɨɬɱɟɬɟ ɨɩɪɟɞɟɥɟɧɧɨɦɭ ɩɹɬɧɭ ɧɚ ɤɚɪɬɟ, ɜ ɩɪɨɝɪɚɦɦɟ ɡɚɩɭɫɤɚɟɬɫɹ ɮɭɧɤɰɢɹ ɨɬɨɛɪɚɠɟɧɢɹ ɧɨɦɟɪɚ ɩɹɬɧɚ ɧɚ ɫɚɦɨɣ ɤɚɪɬɟ, ɚ ɡɚɬɟɦ ɨɧ ɫɪɚɜɧɢɜɚɟɬɫɹ ɫ ɧɨɦɟɪɨɦ («SpotID») ɜ ɨɬɱɟɬɟ. Ⱦɥɹ ɭɥɭɱɲɟɧɢɹ ɬɨɱɧɨɫɬɢ ɫɪɚɜɧɟɧɢɹ ɝɟɥɟɣ ɜ ɩɪɨɝɪɚɦɦɟ ɢɦɟɟɬɫɹ ɮɭɧɤɰɢɹ ɜɵɫɬɚɜɥɟɧɢɹ ɨɩɨɪɧɵɯ ɬɨɱɟɤ, ɛɥɚɝɨɞɚɪɹ ɤɨɬɨɪɨɣ ɜ ɤɚɠɞɨɦ ɝɟɥɟ ɦɨɠɧɨ ɜɵɫɬɚɜɢɬɶ ɨɩɨɪɧɵɟ (ɪɟɮɟɪɟɧɫɧɵɟ) ɬɨɱɤɢ ɧɚ ɩɹɬɧɚɯ, ɤɨɬɨɪɵɟ ɩɪɢɫɭɬɫɬɜɭɸɬ ɧɚ ɨɛɟɢɯ ɷɥɟɤɬɪɨɮɨɪɟɝɪɚɦɦɚɯ. Ɉɩɨɪɧɵɟ ɬɨɱɤɢ 67 ɜɤɥɸɱɚɸɬɫɹ ɜ ɚɧɚɥɢɡ ɢ ɬɨɱɧɨɫɬɶ ɜɨɡɪɚɫɬɚɟɬ. Ʉɨɧɟɱɧɵɦ ɪɟɡɭɥɶɬɚɬɨɦ ɹɜɥɹɟɬɫɹ ɬɪɟɯɦɟɪɧɚɹ ɦɨɞɟɥɶ ɩɹɬɧɚ, ɩɪɟɞɫɬɚɜɥɟɧɧɚɹ ɜ ɜɢɞɟ ɩɢɤɚ, ɤɨɬɨɪɵɣ ɨɬɨɛɪɚɠɚɟɬ ɮɨɪɦɭ ɢ ɨɛɴɟɦ ɩɹɬɧɚ. Ɋɚɛɨɬɚɹ ɫ ɤɨɥɥɟɤɰɢɟɣ ɞɜɭɦɟɪɧɵɯ ɷɥɟɤɬɪɨɮɨɪɟɝɪɚɦɦ, ɦɨɠɧɨ ɨɩɢɫɚɧɧɵɦ ɫɩɨɫɨɛɨɦ ɩɨɫɬɪɨɢɬɶ ɨɛɨɛɳɟɧɧɨɟ, ɫɬɚɧɞɚɪɬɢɡɢɪɨɜɚɧɧɨɟ ɦɨɧɬɚɠɧɨɟ ɢɡɨɛɪɚɠɟɧɢɟ – ɫɨɨɬɜɟɬɫɬɜɭɸɳɭɸ ɛɟɥɤɨɜɭɸ ɤɚɪɬɭ. Ʉɚɤ ɫɥɟɞɭɟɬ ɢɡ ɩɨɥɭɱɟɧɧɵɯ ɪɟɡɭɥɶɬɚɬɨɜ (ɪɢɫ. 3.1–3.4), ɜɨɫɩɪɨɢɡɜɨɞɢɦɨɫɬɶ ɪɟɡɭɥɶɬɚɬɨɜ ɧɚɯɨɞɢɬɫɹ ɧɚ ɜɵɫɨɤɨɦ ɭɪɨɜɧɟ ɢ ɪɚɡɥɢɱɢɹ ɬɪɭɞɧɨ ɨɛɧɚɪɭɠɢɬɶ ɛɟɡ ɢɫɩɨɥɶɡɨɜɚɧɢɹ ɤɨɦɩɶɸɬɟɪɧɨɝɨ ɚɧɚɥɢɡɚ. ɉɪɨɝɪɚɦɦɧɨɟ ɨɛɟɫɩɟɱɟɧɢɟ Phoretix (Nonlinear Dynamics) ɭɜɟɥɢɱɢɜɚɟɬ ɫɩɨɫɨɛɧɨɫɬɶ ɢɡɭɱɟɧɢɹ ɢɡɨɛɪɚɠɟɧɢɣ ɝɟɥɟɣ. Ʉɚɠɞɵɣ ɝɟɥɶ ɩɨɞɜɟɪɝɚɟɬɫɹ ɫɤɚɧɢɪɨɜɚɧɢɸ ɫ ɩɨɥɭɱɟɧɢɟɦ 16-ɛɢɬ ɢɡɨɛɪɚɠɟɧɢɣ, ɱɬɨ ɨɛɟɫɩɟɱɢɜɚɟɬ ɧɚɥɢɱɢɟ ɞɟɬɚɥɢɡɢɪɨɜɚɧɧɨɣ ɢɧɮɨɪɦɚɰɢɢ ɨ ɤɚɠɞɨɦ ɛɟɥɤɨɜɨɦ ɩɹɬɧɟ. Ⱥɧɚɥɢɡɢɪɭɹ ɟɟ, ɤɨɦɩɶɸɬɟɪ ɜɵɞɟɥɹɟɬ ɛɟɥɤɨɜɵɟ ɩɹɬɧɚ ɤɚɠɞɨɝɨ ɝɟɥɹ ɢ ɮɨɪɦɢɪɭɟɬ ɨɛɳɭɸ ɤɚɪɬɢɧɭ ɩɪɨɬɟɨɦɚ. ɇɚɛɨɪ ɛɟɥɤɨɜɵɯ ɩɹɬɟɧ ɮɨɪɦɢɪɭɟɬ ɬ.ɧ. ɛɟɥɤɨɜɵɣ ɩɪɨɮɢɥɶ. Ʉɚɠɞɵɣ ɢɧɞɢɜɢɞɭɚɥɶɧɵɣ ɨɛɪɚɡɟɰ ɜ ɧɚɲɟɦ ɫɥɭɱɚɟ ɞɚɟɬ ɧɟɫɤɨɥɶɤɨ ɨɬɥɢɱɧɵɣ ɧɚɛɨɪ, ɨɩɪɟɞɟɥɹɟɦɵɣ ɤɥɟɬɨɱɧɵɦɢ ɨɫɨɛɟɧɧɨɫɬɹɦɢ ɢɡɭɱɚɟɦɨɝɨ ɨɛɪɚɡɰɚ. ɋɥɟɞɭɸɳɚɹ ɫɨɜɨɤɭɩɧɨɫɬɶ ɪɟɡɭɥɶɬɚɬɨɜ (ɪɢɫ. 3.5–3.10) ɩɪɟɞɫɬɚɜɥɹɟɬ ɫɨɛɨɣ ɧɟ ɱɬɨ ɢɧɨɟ, ɤɚɤ ɢɥɥɸɫɬɪɚɰɢɸ ɦɟɬɨɞɢɱɟɫɤɨɝɨ ɩɨɞɯɨɞɚ, ɩɪɢɝɨɞɧɨɝɨ ɜ ɩɟɪɫɩɟɤɬɢɜɟ ɞɥɹ ɫɪɚɜɧɟɧɢɹ ɞɜɭɯ ɧɚɛɨɪɨɜ ɛɢɨɥɨɝɢɱɟɫɤɢ ɨɬɥɢɱɚɸɳɢɯɫɹ ɨɛɪɚɡɰɨɜ. ɇɚ ɪɢɫ. 3.5–3.6 ɩɪɟɞɫɬɚɜɥɟɧɵ ɪɟɡɭɥɶɬɚɬɵ ɚɧɚɥɢɡɚ ɞɜɭɯ ɩɟɪɜɵɯ ɮɪɚɤɰɢɣ ɞɜɭɯ ɚɥɢɤɜɨɬ. ɇɟɫɦɨɬɪɹ ɧɚ ɬɨ, ɱɬɨ ɞɜɚ ɨɛɪɚɡɰɚ ɩɪɨɢɫɯɨɞɹɬ ɢɡ ɨɞɧɨɣ ɢ ɬɨɣ ɠɟ ɩɪɨɛɵ ɩɭɩɨɜɢɧɧɨɣ ɤɪɨɜɢ, ɞɜɚ ɪɟɡɭɥɶɬɢɪɭɸɳɢɯ ɢɡɨɛɪɚɠɟɧɢɹ ɨɛɧɚɪɭɠɢɜɚɸɬ ɨɩɪɟɞɟɥɟɧɧɵɟ ɨɬɥɢɱɢɹ. Ɉɧɢ ɛɵɥɢ ɩɨɞɜɟɪɝɧɭɬɵ ɤɨɦɩɶɸɬɟɪɧɨɦɭ ɚɧɚɥɢɡɭ, ɚ ɛɟɥɤɨɜɵɟ ɩɪɨɮɢɥɢ ɤɚɠɞɨɝɨ ɨɛɪɚɡɰɚ (Ⱥ ɢ Ȼ) ɫɪɚɜɧɢɜɚɥɢɫɶ ɦɟɬɨɞɨɦ ɧɚɥɨɠɟɧɢɹ ɞɪɭɝ ɧɚ ɞɪɭɝɚ. 68 ɇɚɥɨɠɟɧɢɟ ɢɡɨɛɪɚɠɟɧɢɣ Ⱥ ɢ Ȼ ɞɥɹ ɩɟɪɜɨɣ ɮɪɚɤɰɢɢ Ⱥ Ȼ ɐɜɟɬɨɜɵɟ ɨɬɥɢɱɢɹ ɩɪɢ ɫɪɚɜɧɟɧɢɢ ɨɞɢɧɚɤɨɜɵɯ ɩɹɬɟɧ Ⱥ Ȼ 4-ɤɪɚɬɧɨɟ ɭɜɟɥɢɱɟɧɢɟ ɨɛɴɟɦɚ ɩɹɬɟɧ Ɋɢɫ. 3.5. ɉɟɪɜɚɹ ɮɪɚɤɰɢɹ ɆɇɄ – ɭɝɥɭɛɥɟɧɧɨɟ ɢɡɭɱɟɧɢɟ ɩɪɨɬɟɨɦɧɨɝɨ ɩɪɨɮɢɥɹ ɩɨɩɭɥɹɰɢɢ ɆɇɄ. Ⱦɜɚ ɨɛɪɚɡɰɚ ɩɨ 106 ɤɥɟɬɨɤ ɢɫɫɥɟɞɭɸɬɫɹ ɩɚɪɚɥɥɟɥɶɧɨ ɢ ɚɧɚɥɢɡɢɪɭɸɬɫɹ ɫ ɩɨɦɨɳɶɸ Phoretix software (Nonliner Dynamics). 69 Ɋɟɡɭɥɶɬɢɪɭɸɳɟɟ ɢɡɨɛɪɚɠɟɧɢɟ ɞɚɟɬ ɩɪɟɞɫɬɚɜɥɟɧɢɟ ɨ ɡɨɧɚɯ ɪɚɡɥɢɱɢɣ ɢ ɨɞɧɨɜɪɟɦɟɧɧɨ ɡɨɧɚɯ ɩɨɥɧɨɝɨ ɫɨɜɩɚɞɟɧɢɹ (ɡɟɥɟɧɵɣ ɰɜɟɬ ɧɚɞ ɪɨɡɨɜɵɦ, ɨɛɪɚɡɟɰ Ⱥ ɧɚɞ Ȼ). Ɋɚɡɧɵɟ ɩɹɬɧɚ ɨɛɜɟɞɟɧɵ ɢ ɫɨɩɨɫɬɚɜɥɟɧɵ ɞɥɹ ɞɜɭɯ ɚɥɢɤɜɨɬ. ȼ ɷɬɨɦ ɫɥɭɱɚɟ ɨɛɪɚɡɟɰ Ⱥ ɢɫɩɨɥɶɡɨɜɚɧ ɤɚɤ ɪɟɮɟɪɟɧɫɧɵɣ (ɷɬɚɥɨɧɧɵɣ). ɗɬɚɥɨɧ ɨɩɪɟɞɟɥɟɧ ɩɪɨɝɪɚɦɦɨɣ ɤɚɤ ɝɟɥɶ, ɢɦɟɸɳɢɣ ɧɚɢɛɨɥɶɲɟɟ ɤɨɥɢɱɟɫɬɜɨ ɛɟɥɤɨɜɵɯ ɩɹɬɟɧ. ɇɟɫɨɜɩɚɞɚɸɳɢɟ ɩɹɬɧɚ ɨɛɜɟɞɟɧɵ ɫɟɪɨɣ ɥɢɧɢɟɣ, ɚ ɬɚɦ, ɝɞɟ ɩɹɬɧɚ ɨɛɜɟɞɟɧɵ ɰɜɟɬɚ ɦɨɪɫɤɨɣ ɜɨɥɧɵ ɥɢɧɢɟɣ – ɧɚɛɥɸɞɚɟɬɫɹ ɫɨɜɩɚɞɟɧɢɟ ɞɥɹ ɨɛɨɢɯ ɨɛɪɚɡɰɨɜ. ɉɹɬɧɚ, ɨɛɜɟɞɟɧɧɵɟ ɫɢɧɢɦ, ɹɜɥɹɸɬɫɹ ɩɹɬɧɚɦɢ ɨɛɪɚɡɰɚ Ⱥ, ɤɨɬɨɪɵɟ ɜ ɞɜɚ ɪɚɡɚ ɛɨɥɶɲɟ ɜ ɨɛɴɟɦɟ, ɱɟɦ ɫɨɨɬɜɟɬɫɬɜɭɸɳɢɟ ɩɹɬɧɚ ɜ ɨɛɪɚɡɰɟ Ȼ. ɉɹɬɧɚ, ɨɛɜɟɞɟɧɧɵɟ ɤɪɚɫɧɵɦ, ɜ ɞɜɚ ɪɚɡɚ ɦɟɧɶɲɟ ɩɨ ɨɛɴɟɦɭ ɜ ɨɛɪɚɡɰɟ Ⱥ ɩɨ ɫɪɚɜɧɟɧɢɸ ɫ ɫɨɨɬɜɟɬɫɬɜɭɸɳɢɦɢ ɩɹɬɧɚɦɢ ɨɛɪɚɡɰɚ Ȼ. Ⱥɛɫɨɥɸɬɧɨɟ ɱɢɫɥɨ ɩɹɬɟɧ (ɩɪɟɜɵɲɟɧɢɹ ɢɥɢ ɧɟɞɨɫɬɚɱɚ) ɧɟ ɢɦɟɟɬ ɛɨɥɶɲɨɝɨ ɡɧɚɱɟɧɢɹ, ɨɞɧɚɤɨ ɢɧɬɟɪɟɫɟɧ ɮɚɤɬɨɪ, ɫɩɨɫɨɛɫɬɜɭɸɳɢɣ ɷɬɨɦɭ. Ʉɚɤ ɛɵɥɨ ɨɩɪɟɞɟɥɟɧɨ ɜ ɚɧɚɥɢɬɢɱɟɫɤɨɦ ɷɤɫɩɟɪɢɦɟɧɬɟ (ɪɢɫ. 3.5), ɥɸɛɨɟ ɞɜɭɤɪɚɬɧɨɟ ɩɪɟɜɵɲɟɧɢɟ ɜɟɥɢɱɢɧɵ ɩɹɬɧɚ ɹɜɥɹɟɬɫɹ ɡɧɚɱɢɦɵɦ. Ɏɚɤɬɢɱɟɫɤɢ, ɷɬɨ ɤɪɢɬɟɪɢɣ, ɢɫɩɨɥɶɡɭɟɦɵɣ ɞɥɹ ɨɛɧɚɪɭɠɟɧɢɹ ɩɪɟɞɟɥɨɜ ɡɧɚɱɢɦɨɫɬɢ (ɛɨɥɟɟ ɩɨɞɪɨɛɧɨ ɨɛɫɭɠɞɟɧɨ ɧɢɠɟ). ȼɟɥɢɱɢɧɚ ɩɹɬɧɚ, ɩɨ ɫɭɬɢ, ɨɬɪɚɠɚɟɬ ɨɛɳɟɟ ɤɨɥɢɱɟɫɬɜɨ ɩɪɢɫɭɬɫɬɜɭɸɳɟɝɨ ɛɟɥɤɚ. ɉɪɢ ɚɧɚɥɢɡɟ ɆɇɄ ɢɡ ɨɞɧɨɝɨ ɨɛɪɚɡɰɚ ɩɭɩɨɜɢɧɧɨɣ ɤɪɨɜɢ ɦɵ ɩɨɩɵɬɚɥɢɫɶ ɭɫɬɚɧɨɜɢɬɶ ɩɨɪɨɝ ɡɧɚɱɢɦɨɫɬɢ (ɞɨɫɬɨɜɟɪɧɨɫɬɶ ɪɚɡɥɢɱɢɣ) ɢ ɨɩɪɟɞɟɥɢɬɶ ɪɚɫɯɨɠɞɟɧɢɹ, ɜɵɡɜɚɧɧɵɟ ɢɫɤɥɸɱɢɬɟɥɶɧɨ ɯɨɞɨɦ ɷɤɫɩɟɪɢɦɟɧɬɚ. Ɋɚɡɞɟɥɟɧɢɟ, ɚ ɡɚɬɟɦ ɢɫɫɥɟɞɨɜɚɧɢɟ ɷɬɢɯ ɨɛɪɚɡɰɨɜ ɩɨ ɨɬɞɟɥɶɧɨɫɬɢ ɞɚɟɬ ɜɨɡɦɨɠɧɨɫɬɶ ɭɫɬɚɧɨɜɢɬɶ ɬɨɱɤɭ ɨɬɫɱɟɬɚ ɞɥɹ ɛɭɞɭɳɢɯ ɷɤɫɩɟɪɢɦɟɧɬɨɜ ɫ ɛɢɨɥɨɝɢɱɟɫɤɢ ɪɚɡɥɢɱɧɵɦɢ ɨɛɪɚɡɰɚɦɢ. ɉɨɪɨɝɨɜɨɟ ɡɧɚɱɟɧɢɟ ɢɥɢ ɬ.ɧ. ɩɪɟɞɟɥ ɡɧɚɱɢɦɨɫɬɢ ɨɩɪɟɞɟɥɟɧ ɤɚɤ ɜɟɪɯɧɢɣ ɢ ɧɢɠɧɢɣ ɥɢɦɢɬ ɡɧɚɱɢɦɨɫɬɢ ɢɡɦɟɧɟɧɢɹ ɜɟɥɢɱɢɧɵ ɛɟɥɤɨɜɨɝɨ ɩɹɬɧɚ. 70 ɇɚɥɨɠɟɧɢɟ ɢɡɨɛɪɚɠɟɧɢɣ Ⱥ ɢ Ȼ ɞɥɹ ɜɬɨɪɨɣ ɮɪɚɤɰɢɢ Ⱥ Ȼ ɐɜɟɬɨɜɵɟ ɨɬɥɢɱɢɹ ɩɪɢ ɫɪɚɜɧɟɧɢɢ ɨɞɢɧɚɤɨɜɵɯ ɩɹɬɟɧ Ⱥ Ȼ Ⱥ 3-ɤɪɚɬɧɨɟ ɭɜɟɥɢɱɟɧɢɟ ɨɛɴɟɦɚ ɩɹɬɟɧ Ⱥ Ȼ 1.7-ɤɪɚɬɧɨɟ ɭɦɟɧɶɲɟɧɢɟ ɨɛɴɟɦɚ ɩɹɬɟɧ Ȼ 7-ɤɪɚɬɧɨɟ ɭɜɟɥɢɱɟɧɢɟ ɨɛɴɟɦɚ ɩɹɬɟɧ Ɋɢɫ. 3.6. ȼɬɨɪɚɹ ɮɪɚɤɰɢɹ ɦɨɧɨɧɭɤɥɟɚɪɨɜ – ɭɝɥɭɛɥɟɧɧɨɟ ɢɡɭɱɟɧɢɟ ɩɪɨɬɟɨɦɧɵɯ ɩɪɨɮɢɥɟɣ. 71 Ɂɧɚɱɢɦɵɟ ɢɡɦɟɧɟɧɢɹ – ɬɟ, ɤɨɬɨɪɵɟ ɩɨɹɜɥɹɸɬɫɹ ɜ ɪɟɡɭɥɶɬɚɬɟ ɤɚɤ ɪɟɡɭɥɶɬɚɬ ɛɢɨɥɨɝɢɱɟɫɤɢɯ ɹɜɥɟɧɢɣ, ɚ ɧɟ ɷɤɫɩɟɪɢɦɟɧɬɚɥɶɧɵɯ ɩɪɨɰɟɞɭɪ. ȼ ɫɜɨɸ ɨɱɟɪɟɞɶ, ɩɨɪɨɝɨɜɨɟ ɡɧɚɱɟɧɢɟ ɨɩɪɟɞɟɥɹɟɬɫɹ ɤɚɤ ɤɪɚɬɧɨɫɬɶ ɭɜɟɥɢɱɟɧɢɹ ɢɥɢ ɭɦɟɧɶɲɟɧɢɹ ɜɟɥɢɱɢɧɵ ɩɹɬɧɚ, ɨɬɪɚɠɚɸɳɟɝɨ ɨɛɴɟɦ ɞɚɧɧɨɝɨ ɛɟɥɤɚ. Ⱦɥɹ ɨɩɪɟɞɟɥɟɧɢɹ ɩɪɟɞɟɥɨɜ ɡɧɚɱɢɦɨɫɬɢ, ɜɟɪɯɧɢɣ ɢ ɧɢɠɧɢɣ ɩɪɟɞɟɥɵ ɞɥɹ ɨɛɪɚɡɰɨɜ Ⱥ ɢ Ȼ ɢɡ ɨɞɧɨɣ ɩɪɨɛɵ ɩɭɩɨɜɢɧɧɨɣ ɤɪɨɜɢ ɛɵɥɢ ɭɫɬɚɧɨɜɥɟɧɵ (ɪɢɫ. 3.7–3.10). Ⱥɧɚɥɢɡ 1-ɯ ɮɪɚɤɰɢɣ ɜɵɹɜɢɥ, ɱɬɨ ɜɟɪɯɧɢɣ ɩɪɟɞɟɥ ɭɜɟɥɢɱɟɧɢɹ ɛɟɥɤɨɜɨɝɨ ɩɹɬɧɚ ɨɬ ɨɛɪɚɡɰɚ Ⱥ ɤ ɨɛɪɚɡɰɭ Ȼ ɹɜɥɹɟɬɫɹ 11-ɤɪɚɬɧɵɦ (ɪɢɫ. 3.7). ɇɢɠɧɢɣ ɩɪɟɞɟɥ ɭɦɟɧɶɲɟɧɢɹ ɛɟɥɤɨɜɨɝɨ ɩɹɬɧɚ ɹɜɥɹɟɬɫɹ 4-ɤɪɚɬɧɵɦ (ɪɢɫ. 3.8). Ⱦɥɹ ɦɟɦɛɪɚɧɧɨɣ ɮɪɚɤɰɢɢ ɜɟɪɯɧɢɣ ɩɪɟɞɟɥ ɭɜɟɥɢɱɟɧɢɹ ɨɛɪɚɡɰɚ Ȼ ɩɨ ɫɪɚɜɧɟɧɢɸ ɫ Ⱥ ɹɜɥɹɟɬɫɹ 7-ɤɪɚɬɧɵɦ (ɪɢɫ. 3.9). ɇɢɠɧɢɣ ɩɪɟɞɟɥ (ɞɥɹ ɦɟɦɛɪɚɧɧɵɯ ɮɪɚɤɰɢɣ) ɫɧɢɠɟɧɢɹ ɜɟɥɢɱɢɧɵ ɩɹɬɧɚ ɹɜɥɹɟɬɫɹ 4-ɤɪɚɬɧɵɦ (ɪɢɫ. 3.10). Ⱥ Ȼ Ⱥ Ȼ Ɋɢɫ. 3.7. ɉɟɪɜɚɹ ɮɪɚɤɰɢɹ ɦɨɧɨɧɭɤɥɟɚɪɨɜ – ɜɟɪɯɧɢɣ ɩɪɟɞɟɥ ɡɧɚɱɢɦɨɫɬɢ ɩɪɢ 11-ɤɪɚɬɧɨɦ ɭɜɟɥɢɱɟɧɢɢ ɪɚɡɦɟɪɚ ɩɹɬɧɚ. 72 Ⱥ Ȼ Ⱥ Ȼ Ɋɢɫ. 3.8. ɉɟɪɜɚɹ ɮɪɚɤɰɢɹ ɆɇɄ – ɧɢɠɧɢɣ ɩɪɟɞɟɥ ɡɧɚɱɢɦɨɫɬɢ ɩɪɢ 4ɤɪɚɬɧɨɦ ɭɦɟɧɶɲɟɧɢɢ ɪɚɡɦɟɪɚ ɩɹɬɧɚ Ⱥ Ȼ Ⱥ Ȼ Ɋɢɫ. 3.9. ȼɬɨɪɚɹ ɮɪɚɤɰɢɹ ɆɇɄ – ɜɟɪɯɧɢɣ ɩɪɟɞɟɥ ɡɧɚɱɢɦɨɫɬɢ ɩɪɢ 11ɤɪɚɬɧɨɦ ɭɜɟɥɢɱɟɧɢɢ ɪɚɡɦɟɪɚ ɩɹɬɧɚ 73 Ⱥ Ȼ Ⱥ Ȼ Ɋɢɫ. 3.10. ȼɬɨɪɚɹ ɮɪɚɤɰɢɹ ɆɇɄ – ɧɢɠɧɢɣ ɩɪɟɞɟɥ ɡɧɚɱɢɦɨɫɬɢ ɩɪɢ 4ɤɪɚɬɧɨɦ ɭɦɟɧɶɲɟɧɢɢ ɪɚɡɦɟɪɚ ɩɹɬɧɚ Ɍɚɤɢɦ ɨɛɪɚɡɨɦ, ɦɵ ɩɨɥɚɝɚɟɦ, ɱɬɨ ɞɥɹ ɞɚɥɶɧɟɣɲɢɯ ɚɧɚɥɢɡɨɜ ɩɨɪɨɝɨɜɵɟ ɜɟɥɢɱɢɧɵ ɩɪɟɞɟɥɨɜ ɡɧɚɱɢɦɨɫɬɢ ɞɥɹ ɛɟɥɤɨɜɵɯ ɢɡɦɟɧɟɧɢɣ, ɮɢɤɫɢɪɭɟɦɵɯ ɩɨ ɜɟɥɢɱɢɧɟ ɩɹɬɧɚ, ɫɥɟɞɭɟɬ ɭɫɬɚɧɚɜɥɢɜɚɬɶ ɚɧɚɥɨɝɢɱɧɵɦ ɨɛɪɚɡɨɦ. 3.2.2 ɉɨɩɭɥɹɰɢɹ CD34+ ɝɟɦɨɩɨɷɬɢɱɟɫɤɢɯ ɫɬɜɨɥɨɜɵɯ ɤɥɟɬɨɤ ɉɟɪɜɵɟ ɩɨɩɵɬɤɢ ɨɯɚɪɚɤɬɟɪɢɡɨɜɚɬɶ CD34+ȽɋɄ ɫ ɢɫɩɨɥɶɡɨɜɚɧɢɟɦ ɦɟɬɨɞɨɜ ɩɪɨɬɟɨɦɢɤɢ ɛɵɥɢ ɨɝɪɚɧɢɱɟɧɵ ɧɢɡɤɢɦ ɫɨɞɟɪɠɚɧɢɟɦ ɛɟɥɤɚ (106 ɤɥɟɬɨɤ). ɉɨɥɭɱɟɧɧɵɟ ɪɟɡɭɥɶɬɚɬɵ ɢɥɥɸɫɬɪɢɪɭɸɬɫɹ ɧɢɠɟ (ɪɢɫ. 3.11). ȼɵɞɟɥɟɧɢɟ CD34+ȽɋɄ ɢɡ ɨɛɪɚɡɰɚ ɩɭɩɨɜɢɧɧɨɣ ɤɪɨɜɢ – ɫɥɨɠɧɚɹ ɩɪɨɰɟɞɭɪɚ. ȼɵɯɨɞ ɱɚɫɬɨ ɹɜɥɹɟɬɫɹ ɧɢɡɤɢɦ ɢ ɞɚɟɬ ɧɟɞɨɫɬɚɬɨɱɧɨɟ ɤɨɥɢɱɟɫɬɜɨ ɤɥɟɬɨɤ. ɗɬɨ ɦɚɥɨɟ ɤɨɥɢɱɟɫɬɜɨ ɤɥɟɬɨɤ ɩɪɢɜɨɞɢɬ ɤ ɧɢɡɤɨɣ ɱɭɜɫɬ- 74 ɜɢɬɟɥɶɧɨɫɬɢ ɩɪɨɬɟɨɦɧɨɝɨ ɚɧɚɥɢɡɚ. ɉɪɨɜɟɞɟɧɧɵɟ ɧɚ ɤɥɟɬɤɚɯ ɨɫɬɟɨɫɚɪɤɨɦɵ ɷɤɫɩɟɪɢɦɟɧɬɵ ɩɨɤɚɡɚɥɢ, ɱɬɨ ɜɟɪɯɧɢɟ ɩɪɟɞɟɥɵ ɱɭɜɫɬɜɢɬɟɥɶɧɨɫɬɢ ɞɨɫɬɢɝɚɸɬɫɹ ɩɪɢ ɚɧɚɥɢɡɟ ɨɛɪɚɡɰɚ, ɫɨɞɟɪɠɚɳɟɝɨ 3×106 ɤɥɟɬɨɤ. Ⱦɚɥɶɧɟɣɲɢɟ ɢɫɫɥɟɞɨɜɚɧɢɹ ɧɚ ɆɇɄ ɭɫɬɚɧɨɜɢɥɢ, ɱɬɨ ɤɨɥɢɱɟɫɬɜɨ 1×106 ɤɥɟɬɨɤ ɹɜɥɹɸɬɫɹ ɢɞɟɚɥɶɧɵɦ ɧɚɛɨɪɨɦ ɞɥɹ ɞɢɧɚɦɢɱɟɫɤɨɝɨ ɩɪɨɦɟɠɭɬɤɚ. ɗɬɢ ɨɛɫɬɨɹɬɟɥɶɫɬɜɚ ɛɵɥɢ ɭɱɬɟɧɵ ɩɪɢ ɢɫɫɥɟɞɨɜɚɧɢɢ CD34+ ɤɥɟɬɨɤ. Ɍɟɦ ɧɟ ɦɟɧɟɟ, ɩɨɥɭɱɟɧɧɵɟ 2 ɝɟɥɹ ɞɥɹ CD34+ ɤɥɟɬɨɤ ɭɤɚɡɵɜɚɸɬ ɧɚ ɬɨ, ɱɬɨ ɤɨɥɢɱɟɫɬɜɨ 1×106 ɤɥɟɬɨɤ ɹɜɥɹɟɬɫɹ ɧɟɞɨɫɬɚɬɨɱɧɵɦ. Ⱦɜɚ ɨɛɪɚɡɰɚ (Ⱥ ɢ Ȼ), ɜɵɞɟɥɟɧɧɵɟ ɢɡ ɞɜɭɯ ɪɚɡɧɵɯ ɩɪɨɛ ɩɭɩɨɜɢɧɧɨɣ ɤɪɨɜɢ, ɛɵɥɢ ɩɪɨɚɧɚɥɢɡɢɪɨɜɚɧɵ (ɪɢɫ. 3.11). Ɉɛɪɚɡɟɰ Ⱥ ɫɨɞɟɪɠɚɥ 1×106 CD34+ ɤɥɟɬɨɤ, ɚ ɨɛɪɚɡɟɰ ȼ – 1,4×106 CD34+ ɤɥɟɬɨɤ. ɉɪɟɞɫɬɚɜɥɹɟɬɫɹ, ɱɬɨ 1-ɹ ɮɪɚɤɰɢɹ ɨɛɪɚɡɰɚ Ȼ ɢɦɟɥɚ ɧɟɫɤɨɥɶɤɨ ɛɨɥɶɲɟɟ ɤɨɥɢɱɟɫɬɜɨ ɛɟɥɤɨɜɵɯ ɩɹɬɟɧ, ɱɟɦ ɭ ɨɛɪɚɡɰɚ Ⱥ, ɧɨ ɷɬɨ ɧɟ ɧɟ ɫɨɜɫɟɦ ɭɛɟɞɢɬɟɥɶɧɨ, ɬɚɤ ɤɚɤ ɨɛɳɟɟ ɤɨɥɢɱɟɫɬɜɨ ɩɹɬɟɧ ɫɥɢɲɤɨɦ ɦɚɥɨ. ɗɬɨ ɧɚɲɥɨ ɫɜɨɟ ɩɨɞɬɜɟɪɠɞɟɧɢɟ ɢ ɩɪɢ ɫɪɚɜɧɟɧɢɢ ɦɨɧɬɚɠɧɵɯ ɢɡɨɛɪɚɠɟɧɢɣ ɩɟɪɜɵɯ ɮɪɚɤɰɢɣ ɨɛɪɚɡɰɚ ɫ CD34+ ɤɥɟɬɤɚɦɢ (ɪɢɫ. 3.13) ɢ ɨɛɪɚɡɰɚ ɫ ɆɇɄ (ɪɢɫ. 3.12). Ɉɱɟɜɢɞɧɨ, ɱɬɨ ɩɹɬɧɚ, ɜɵɹɜɥɟɧɧɵɟ ɩɪɨɝɪɚɦɦɨɣ Phoretix ɞɥɹ ɨɛɪɚɡɰɚ ɫ CD34+ ɤɥɟɬɤɚɦɢ, ɧɚɯɨɞɹɬɫɹ ɧɚ ɭɪɨɜɧɟ ɧɢɠɧɟɝɨ ɩɪɟɞɟɥɚ ɱɭɜɫɬɜɢɬɟɥɶɧɨɫɬɢ. Ɍɚɤɢɦ ɨɛɪɚɡɨɦ, ɤɨɥɢɱɟɫɬɜɨ ɛɟɥɤɚ, ɩɪɢɫɭɬɫɬɜɭɸɳɟɝɨ ɜ ɨɛɪɚɡɰɟ ɫ 1×106 CD34 + ɤɥɟɬɨɤ, ɧɢɠɟ, ɱɟɦ ɜ ɨɛɪɚɡɰɟ ɫ 1×106 ɆɇɄ. Ɉɞɧɚ ɢɡ ɜɨɡɦɨɠɧɵɯ ɩɪɢɱɢɧ ɷɬɨɝɨ – ɩɨɬɟɪɹ ɛɟɥɤɚ ɧɚ ɫɬɚɞɢɹɯ ɩɨɞɝɨɬɨɜɤɢ ɨɛɪɚɡɰɨɜ ɤ ɚɧɚɥɢɡɭ. Ⱦɚɠɟ ɫ ɭɱɟɬɨɦ ɬɨɝɨ, ɱɬɨ ɤɨɦɩɶɸɬɟɪɧɵɣ ɚɧɚɥɢɡ ɩɨɡɜɨɥɹɟɬ ɨɛɧɚɪɭɠɢɜɚɬɶ ɧɢɡɤɢɟ ɤɨɧɰɟɧɬɪɚɰɢɢ ɢɫɫɥɟɞɭɟɦɵɯ ɫɨɟɞɢɧɟɧɢɣ ɢ ɜɵɹɜɥɹɬɶ ɛɟɥɤɨɜɵɟ ɩɹɬɧɚ, ɨɬɧɨɫɢɬɟɥɶɧɨɟ ɫɨɞɟɪɠɚɧɢɟ ɛɟɥɤɚ ɨɤɚɡɚɥɨɫɶ ɛɥɢɡɤɢɦ ɤ ɩɨɪɨɝɭ ɱɭɜɫɬɜɢɬɟɥɶɧɨɫɬɢ, ɱɬɨ ɫɥɟɞɭɟɬ ɢɡ ɦɨɧɬɚɠɧɨɝɨ ɚɧɚɥɢɡɚ ɝɟɥɟɣ, ɩɪɟɞɫɬɚɜɥɟɧɧɨɝɨ ɧɚ ɪɢɫ. 3.12–3.13. 75 Ȼ. Ȼ. Ȼ. Ȼ. Ɋɢɫ. 3.11. 2D-ɢɡɨɛɪɚɠɟɧɢɹ CD34+ ȽɋɄ ɱɟɬɵɪɟɯ ɤɥɟɬɨɱɧɵɯ ɮɪɚɤɰɢɣ (1-ɹ ɮɪɚɤɰɢɹ A. 1-ɹ ɮɪɚɤɰɢɹ Ȼ. 2-ɹ ɮɪɚɤɰɢɹ A. 2-ɹ ɮɪɚɤɰɢɹ Ȼ. 3-ɹ ɮɪɚɤɰɢɹ Ⱥ. 3-ɹ ɮɪɚɤɰɢɹ Ȼ. 4-ɹ ɮɪɚɤɰɢɹ A. 4-ɹ ɮɪɚɤɰɢɹ Ȼ). 76 Ɋɢɫ. 3.12. ɉɟɪɜɚɹ ɮɪɚɤɰɢɹ CD34+ ȽɋɄ (106 ɤɥɟɬɨɤ) – ɦɨɧɬɚɠɧɚɹ ɜɢɡɭɚɥɢɡɚɰɢɹ Ɋɢɫ. 3.13. ɉɟɪɜɚɹ ɮɪɚɤɰɢɹ ɆɇɄ (106 ɤɥɟɬɨɤ) – ɦɨɧɬɚɠɧɚɹ ɜɢɡɭɚɥɢɡɚɰɢɹ 77 Ɋɢɫ. 3.14. ɉɟɪɜɚɹ ɮɪɚɤɰɢɹ CD34+ȽɋɄ (2×106 ɤɥɟɬɨɤ) – ɝɟɥɶ ɢ ɟɝɨ ɦɨɧɬɚɠɧɚɹ ɜɢɡɭɚɥɢɡɚɰɢɹ ɉɨɜɬɨɪɧɵɣ ɚɧɚɥɢɡ ɨɛɪɚɡɰɚ CD34+ȽɋɄ ɛɵɥ ɩɪɨɜɟɞɟɧ ɞɥɹ ɞɜɨɣɧɨɝɨ ɤɨɥɢɱɟɫɬɜɚ (2×106) ɤɥɟɬɨɤ. ɂɡɨɛɪɚɠɟɧɢɹ ɝɟɥɹ ɞɥɹ ɩɟɪɜɨɣ ɮɪɚɤɰɢɢ ɤɥɟɬɨɤ ɩɪɟɞɫɬɚɜɥɟɧɵ ɧɚ ɪɢɫ. 3.14. Ɉɱɟɜɢɞɧɨ, ɱɬɨ ɪɚɛɨɬɚ ɫ ɞɜɨɣɧɵɦ ɤɨɥɢɱɟɫɬɜɨɦ ɤɥɟɬɨɤ ɨɛɟɫɩɟɱɢɜɚɥɚ ɩɪɨɬɟɨɦɧɵɣ ɚɧɚɥɢɡ ɞɨɫɬɚɬɨɱɧɵɦ ɤɨɥɢɱɟɫɬɜɨɦ ɦɚɬɟɪɢɚɥɚ. 78 ɇɚ ɪɢɫ. 3.15–3.16 ɩɪɟɞɫɬɚɜɥɟɧɵ ɨɛɨɛɳɟɧɧɵɟ ɪɟɡɭɥɶɬɚɬɵ ɚɧɚɥɢɡɚ ɩɪɨɬɟɨɦɧɵɯ ɩɪɨɮɢɥɟɣ ɢ ɢɞɟɧɬɢɮɢɤɚɰɢɢ ɛɟɥɤɨɜ ɩɨ ɜɚɠɧɟɣɲɢɦ ɛɟɥɤɚɦ ɬɪɟɯ ɮɪɚɤɰɢɣ CD34+ ȽɋɄ. 1-ɚɹ ȼɟɪɨɹɬɧɨɫɬɶ ɉɨɤɪɵɬɢɟɉɹɬɧɨ ɂɞɟɧɬɢɮɢɰɢɪɨɜɚɧɧɵɟɛɟɥɤɢ ɋɨɜɩɚɞɟɧɢɹ ɫ ɜɟɪɨɹɬɧɨɫɬɶɸ ɛɨɥɟɟ 50% 10 ɦɚɤɫɢɦɚɥɶɧɵɯ ɫɨɜɩɚɞɟɧɢɣ 2-ɚɹ ȼɟɪɨɹɬɧɨɫɬɶ ɉɨɤɪɵɬɢɟ ɉɹɬɧɨ ɂɞɟɧɬɢɮɢɰɢɪɨɜɚɧɧɵɟɛɟɥɤɢ ɋɨɜɩɚɞɟɧɢɹ ɫ ɜɟɪɨɹɬɧɨɫɬɶɸ ɛɨɥɟɟ 50% 10 ɦɚɤɫɢɦɚɥɶɧɵɯ ɫɨɜɩɚɞɟɧɢɣ 3-ɹ ȼɟɪɨɹɬɧɨɫɬɶɉɨɤɪɵɬɢɟ ɉɹɬɧɨ ɂɞɟɧɬɢɮɢɰɢɪɨɜɚɧɧɵɟɛɟɥɤɢ 10 ɦɚɤɫɢɦɚɥɶɧɵɯ ɫɨɜɩɚɞɟɧɢɣ ɋɨɜɩɚɞɟɧɢɹ ɫ ɜɟɪɨɹɬɧɨɫɬɶɸ ɛɨɥɟɟ 50% Ɋɢɫ. 3.15. ȼɚɠɧɟɣɲɢɟ ɛɟɥɤɨɜɵɟ ɫɬɪɭɤɬɭɪɵ ɞɥɹ ɬɪɟɯ ɮɪɚɤɰɢɣ CD34+ȽɋɄ (A ɩɨɜɬɨɪɧɨɫɬɶ) 79 1-ɚɹ ȼɟɪɨɹɬɧɨɫɬɶ ɉɨɤɪɵɬɢɟ ɉɹɬɧɨ ɂɞɟɧɬɢɮɢɰɢɪɨɜɚɧɧɵɟ ɛɟɥɤɢ 10 ɦɚɤɫɢɦɚɥɶɧɵɯ ɫɨɜɩɚɞɟɧɢɣ ɋɨɜɩɚɞɟɧɢɹ ɫ ɜɟɪɨɹɬɧɨɫɬɶɸ ɛɨɥɟɟ 50% 2-ɚɹ ȼɟɪɨɹɬɧɨɫɬɶ ɉɨɤɪɵɬɢɟ ɉɹɬɧɨ ɂɞɟɧɬɢɮɢɰɢɪɨɜɚɧɧɵɟ ɛɟɥɤɢ 10 ɦɚɤɫɢɦɚɥɶɧɵɯ ɫɨɜɩɚɞɟɧɢɣ ɋɨɜɩɚɞɟɧɢɹ ɫ ɜɟɪɨɹɬɧɨɫɬɶɸ ɛɨɥɟɟ 50% 3-ɹ ȼɟɪɨɹɬɧɨɫɬɶ ɉɨɤɪɵɬɢɟ 10 ɦɚɤɫɢɦɚɥɶɧɵɯ ɫɨɜɩɚɞɟɧɢɣ ɉɹɬɧɨ ɂɞɟɧɬɢɮɢɰɢɪɨɜɚɧɧɵɟ ɛɟɥɤɢ ɋɨɜɩɚɞɟɧɢɹ ɫ ɜɟɪɨɹɬɧɨɫɬɶɸ ɛɨɥɟɟ 50% Ɋɢɫ. 3.16. ȼɚɠɧɟɣɲɢɟ ɛɟɥɤɨɜɵɟ ɫɬɪɭɤɬɭɪɵ ɞɥɹ ɬɪɟɯ ɮɪɚɤɰɢɣ CD34+ ȽɋɄ (Ȼ ɩɨɜɬɨɪɧɨɫɬɶ) ɉɪɢɱɢɧɚ ɢɫɩɨɥɶɡɨɜɚɧɢɹ ɧɚɦɢ 50%-ɤɪɢɬɟɪɢɹ (ɜɟɪɨɹɬɧɨɫɬɧɨɝɨ ɤɨɷɮɮɢɰɢɟɧɬɚ ɞɨɫɬɨɜɟɪɧɨɫɬɢ – ɩɪɨɰɟɧɬɧɨɝɨ ɩɨɤɪɵɬɢɹ ɚɦɢɧɨɤɢɫɥɨɬɧɨɣ ɩɨɫɥɟɞɨɜɚɬɟɥɶɧɨɫɬɢ ɛɟɥɤɚ ɢɞɟɧɬɢɮɢɰɢɪɨɜɚɧɧɵɦɢ ɩɟɩɬɢɞɚɦɢ) ɢɥɢ ɞɚɠɟ ɛɨɥɟɟ ɡɧɚɱɢɦɨɝɨ ɨɛɴɹɫɧɹɟɬɫɹ ɬɟɦ, ɱɬɨ ɱɟɦ ɜɵɲɟ ɞɚɧɧɚɹ ɜɟɥɢɱɢɧɚ, ɬɟɦ ɞɨɫɬɨɜɟɪɧɟɟ ɢɞɟɧɬɢɮɢɤɚɰɢɹ ɛɟɥɤɨɜ. ɗɬɨ ɹɜɥɹɟɬɫɹ ɦɟɪɨɣ ɭɜɟɪɟɧɧɨɫɬɢ ɜ ɬɨɦ, ɱɬɨ id ɛɟɥɤɚ ɹɜɥɹɟɬɫɹ ɜɟɥɢɱɢɧɨɣ ɢɫɬɢɧɧɨɣ (ɫ ɜɟɪɨɹɬɧɨɫɬɶɸ >50%), ɚ ɧɟ ɨɲɢɛɨɱɧɨɣ. 80 ȼɚɠɧɟɣɲɢɟ ɛɟɥɤɨɜɵɟ ɫɬɪɭɤɬɭɪɵ (ɜɟɪɨɹɬɧɨɫɬɧɵɣ ɤɨɷɮɮɢɰɢɟɧɬ ɞɨɫɬɨɜɟɪɧɨɫɬɢ 50% ɢ ɜɵɲɟ), ɜɵɪɚɠɟɧɧɵɟ ɤɚɤ ɤɨɥɢɱɟɫɬɜɨ ɢɞɟɧɬɢɮɢɰɢɪɨɜɚɧɧɵɯ ɜ ɪɚɡɧɵɯ ɫɬɪɭɤɬɭɪɚɯ ɤɥɟɬɤɢ ɛɟɥɤɨɜ, ɢɫɩɨɥɶɡɨɜɚɧɵ ɞɥɹ ɢɥɥɸɫɬɪɚɰɢɢ ɜ ɤɚɱɟɫɬɜɟ ɩɪɢɦɟɪɚ ɚɧɚɥɢɡɚ, ɤɨɬɨɪɵɣ ɦɨɠɟɬ ɛɵɬɶ ɜɵɩɨɥɧɟɧ ɡɚ ɫɱɟɬ ɨɛɴɟɞɢɧɟɧɢɹ ɪɟɡɭɥɶɬɚɬɨɜ ɦɚɫɫ-ɫɩɟɤɬɪɨɦɟɬɪɢɢ (ɪɢɫ. 3.17–3.18). Ɋɢɫ. 3.17. ȼɚɠɧɟɣɲɢɟ ɛɟɥɤɨɜɵɟ ɫɬɪɭɤɬɭɪɵ ɜ ɬɟɪɦɢɧɚɯ ɤɥɟɬɨɱɧɨɣ ɤɨɦɩɚɪɬɦɟɧɬɚɥɢɡɚɰɢɢ. Ƚɪɚɮɢɱɟɫɤɨɟ ɩɪɟɞɫɬɚɜɥɟɧɢɟ ɨɬɧɨɫɢɬɟɥɶɧɨɣ ɥɨɤɚɥɢɡɚɰɢɢ ɛɟɥɤɨɜ ɜ ȽɋɄ Ɋɢɫ. 3.18. ȼɚɠɧɟɣɲɢɟ ɛɟɥɤɨɜɵɟ ɫɬɪɭɤɬɭɪɵ ɜ ɬɟɪɦɢɧɚɯ ɤɥɟɬɨɱɧɨɣ ɤɨɦɩɚɪɬɦɟɧɬɚɥɢɡɚɰɢɢ. ɋɯɟɦɚɬɢɱɟɫɤɨɟ ɩɪɟɞɫɬɚɜɥɟɧɢɟ ɨɬɧɨɫɢɬɟɥɶɧɨɣ ɥɨɤɚɥɢɡɚɰɢɢ ɛɟɥɤɨɜ ɜ ȽɋɄ. 81 Ʉɚɤ ɩɨɥɚɝɚɟɬ Tao [86], ɭ ȽɋɄ ɛɟɥɤɢ ɥɨɤɚɥɢɡɨɜɚɧɵ ɜ ɨɫɧɨɜɧɨɦ ɜɨɤɪɭɝ ɹɞɪɚ ɢ ɜ ɰɢɬɨɩɥɚɡɦɚɬɢɱɟɫɤɨɦ ɞɨɦɟɧɟ. ɗɬɨ ɫɨɨɬɜɟɬɫɬɜɭɟɬ ɝɢɩɨɬɟɡɟ, ɱɬɨ ɧɟɡɪɟɥɵɟ ɫɬɜɨɥɨɜɵɟ ɤɥɟɬɤɢ ɚɤɬɢɜɧɨ ɜɨɜɥɟɤɚɸɬɫɹ ɜ ɫɢɧɬɟɡ ɛɟɥɤɚ ɢ, ɤɚɤ ɪɟɡɭɥɶɬɚɬ, ɚɤɤɭɦɭɥɢɪɭɸɬ ɛɨɥɶɲɢɟ ɤɨɥɢɱɟɫɬɜɚ ɛɟɥɤɚ ɪɹɞɨɦ ɫ ɬɪɚɧɫɥɹɰɢɨɧɧɵɦɢ ɡɨɧɚɦɢ ɤɥɟɬɤɢ. Ʉɨɧɟɱɧɨ, ɞɥɹ ɩɨɞɬɜɟɪɠɞɟɧɢɹ ɷɬɨɣ ɝɢɩɨɬɟɡɵ ɬɪɟɛɭɸɬɫɹ ɞɨɩɨɥɧɢɬɟɥɶɧɵɟ ɢɫɫɥɟɞɨɜɚɧɢɹ, ɧɨ ɩɟɪɜɵɣ ɲɚɝ ɜ ɷɬɨɦ ɧɚɩɪɚɜɥɟɧɢɢ ɭɠɟ ɫɞɟɥɚɧ ɫ ɩɨɦɨɳɶɸ ɢɦɟɧɧɨ ɩɪɨɬɟɨɦɢɤɢ. 3.3. ɂɡɭɱɟɧɢɟ ɚɫɫɨɰɢɚɰɢɢ ɩɪɨɬɟɨɦɢɱɟɫɤɨɝɨ ɩɪɨɮɢɥɹ ɫ ɚɬɟɪɨɫɤɥɟɪɨɡɨɦ Ɉɱɟɜɢɞɧɨ, ɱɬɨ ɜɵɹɜɥɟɧɢɟ ɮɭɧɤɰɢɨɧɚɥɶɧɨɣ ɫɜɹɡɢ ɦɟɠɞɭ ɚɬɟɪɨɫɤɥɟɪɨɬɢɱɟɫɤɢɦɢ ɩɨɪɚɠɟɧɢɹɦɢ ɢ ɩɪɨɬɟɨɦɢɱɟɫɤɢɦ ɩɪɨɮɢɥɟɦ ɢɧɬɢɦɵ ɚɨɪɬɵ ɱɟɥɨɜɟɤɚ ɢɦɟɟɬ ɢɫɤɥɸɱɢɬɟɥɶɧɨɟ ɡɧɚɱɟɧɢɟ ɞɥɹ ɩɨɧɢɦɚɧɢɹ ɢɧɢɰɢɢɪɭɸɳɢɯ ɩɪɢɱɢɧ ɜɨɡɧɢɤɧɨɜɟɧɢɹ ɚɬɟɪɨɫɤɥɟɪɨɡɚ. ɍɠɟ ɫɨɡɞɚɧɵ ɛɚɡɵ ɞɚɧɧɵɯ ɩɨ ɫɨɬɧɹɦ ɛɟɥɤɨɜ ɩɪɨɬɟɨɦɚ ɦɢɨɤɚɪɞɚ, ɭɪɨɜɧɢ ɤɨɬɨɪɵɯ ɢɡɦɟɧɹɸɬɫɹ ɩɪɢ ɫɟɪɞɟɱɧɨ-ɫɨɫɭɞɢɫɬɨɣ ɩɚɬɨɥɨɝɢɢ, ɤɚɤ ɨɫɬɪɨɣ, ɬɚɤ ɢ ɯɪɨɧɢɱɟɫɤɨɣ [17]. Ɉɞɧɚɤɨ ɞɨ ɧɚɫɬɨɹɳɟɝɨ ɜɪɟɦɟɧɢ ɥɢɲɶ ɜ ɨɱɟɧɶ ɧɟɛɨɥɶɲɨɦ ɤɨɥɢɱɟɫɬɜɟ ɪɚɛɨɬ ɛɵɥɢ ɢɫɫɥɟɞɨɜɚɧɵ ɛɟɥɤɢ, ɜɵɞɟɥɟɧɧɵɟ ɢɡ ɚɬɟɪɨɫɤɥɟɪɨɬɢɱɟɫɤɢɯ ɛɥɹɲɟɤ ɚɨɪɬɵ ɱɟɥɨɜɟɤɚ [29, 31, 56]. Ɉɫɨɛɵɣ ɢɧɬɟɪɟɫ ɩɪɢ ɩɪɨɜɟɞɟɧɢɢ ɧɚɲɟɝɨ ɢɫɫɥɟɞɨɜɚɧɢɹ ɩɪɟɞɫɬɚɜɥɹɥɢ ɩɪɨɬɟɨɦɧɵɟ ɩɪɨɮɢɥɢ ɢɧɬɢɦɵ ɢ ɦɟɞɢɢ ɚɪɬɟɪɢɣ ɩɪɢ ɪɚɡɧɵɯ ɫɬɚɞɢɹɯ ɚɬɟɪɨɫɤɥɟɪɨɬɢɱɟɫɤɨɝɨ ɩɨɪɚɠɟɧɢɹ. ɇɚ ɪɢɫ. 3.19 ɩɪɟɞɫɬɚɜɥɟɧɵ 2D-ɷɥɟɤɬɪɨɮɨɪɟɝɪɚɦɦɵ ɷɤɫɬɪɚɤɬɨɜ ɛɟɥɤɚ ɢɡ ɨɛɪɚɡɰɨɜ ɬɤɚɧɢ ɧɟɩɨɪɚɠɟɧɧɨɣ ɢɧɬɢɦɵ ɚɨɪɬɵ ɱɟɥɨɜɟɤɚ ɢ ɥɢɩɨɮɢɛɪɨɡɧɨɣ ɛɥɹɲɤɢ, ɩɨɥɭɱɟɧɧɵɯ ɢɡ ɨɞɧɨɝɨ ɚɭɬɨɩɫɢɣɧɨɝɨ ɦɚɬɟɪɢɚɥɚ. Ɉɱɟɜɢɞɧɨ, ɱɬɨ ɩɨɥɭɱɟɧɧɵɟ ɩɪɨɬɟɨɦɧɵɟ ɩɪɨɮɢɥɢ ɢɦɟɸɬ ɫɭɳɟɫɬɜɟɧɧɵɟ ɤɚɱɟɫɬɜɟɧɧɵɟ ɢ ɤɨɥɢɱɟɫɬɜɟɧɧɵɟ ɪɚɡɥɢɱɢɹ. ȼ ɱɚɫɬɧɨɫɬɢ, ɜ ɥɢɩɨɮɢɛɪɨɡɧɨɣ ɛɥɹɲɤɟ (ɧɚɢɛɨɥɟɟ ɚɤɬɢɜɧɨɣ ɢ ɭɝɪɨɠɚɸɳɟɣ ɠɢɡɧɢ ɮɨɪɦɟ ɚɬɟɪɨɫɤɥɟɪɨɬɢɱɟɫɤɨɝɨ ɩɨɪɚɠɟɧɢɹ) ɩɨ ɫɪɚɜɧɟɧɢɸ ɫ ɧɨɪɦɨɣ ɨɬɦɟɱɚɟɬɫɹ 82 ɩɪɟɨɛɥɚɞɚɧɢɟ ɛɟɥɤɨɜ ɫ ɦɚɫɫɨɣ 75-90 ɤȾɚ ɢ ɢɡɨɷɥɟɤɬɪɢɱɟɫɤɨɣ ɬɨɱɤɨɣ ɜ ɢɧɬɟɪɜɚɥɟ pH ɨɬ 5 ɞɨ 7; ɛɟɥɤɨɜ ɫ ɦɚɫɫɨɣ ɨɤɨɥɨ 65 ɤȾɚ ɢ ɢɡɨɷɥɟɤɬɪɢɱɟɫɤɨɣ ɬɨɱɤɨɣ ɜ ɢɧɬɟɪɜɚɥɟ ɪɇ ɨɬ 4,5 ɞɨ 5,5. ɉɪɢ ɷɬɨɦ ɜ ɥɢɩɨɮɢɛɪɨɡɧɨɣ ɛɥɹɲɤɟ ɭɦɟɧɶɲɟɧɨ ɫɨɞɟɪɠɚɧɢɟ ɛɟɥɤɨɜ ɫ ɦɚɫɫɨɣ ɨɤɨɥɨ 70 ɤȾɚ ɢ ɨɤɨɥɨ 40 ɤȾɚ ɢ ɢɡɨɷɥɟɤɬɢɱɟɫɤɨɣ ɬɨɱɤɨɣ ɜ ɢɧɬɟɪɜɚɥɟ ɪɇ ɨɬ 4,5 ɞɨ 5,0. Ɍɚɤɠɟ ɫɭɳɟɫɬɜɭɸɬ ɦɧɨɝɨɱɢɫɥɟɧɧɵɟ ɦɟɧɟɟ ɜɵɪɚɠɟɧɧɵɟ ɪɚɡɥɢɱɢɹ. ɇɚ ɪɢɫ. 3.20 ɩɪɟɞɫɬɚɜɥɟɧɵ ɷɥɟɤɬɪɨɮɨɪɟɝɪɚɦɦɵ ɷɤɫɬɪɚɤɬɨɜ ɛɟɥɤɚ ɢɡ ɨɛɪɚɡɰɨɜ ɬɤɚɧɢ ɢɧɬɢɦɵ, ɩɨɥɭɱɟɧɧɨɣ ɢɡ ɚɭɬɨɩɫɢɣɧɨɝɨ ɦɚɬɟɪɢɚɥɚ, ɜ ɤɨɬɨɪɨɦ ɩɪɢɫɭɬɫɬɜɨɜɚɥɢ, ɧɚɪɹɞɭ ɫ ɧɟɩɨɪɚɠɟɧɧɵɦɢ ɭɱɚɫɬɤɚɦɢ, ɜɫɟ ɢɡɭɱɚɟɦɵɟ ɜɢɞɵ ɚɬɟɪɨɫɤɥɟɪɨɬɢɱɟɫɤɢɯ ɩɨɪɚɠɟɧɢɣ (ɧɚɱɚɥɶɧɵɟ ɩɨɪɚɠɟɧɢɹ, ɠɢɪɨɜɚɹ ɩɨɥɨɫɚ, ɥɢɩɨɮɢɛɪɨɡɧɚɹ ɛɥɹɲɤɚ, ɮɢɛɪɨɡɧɚɹ ɛɥɹɲɤɚ). Ɉɱɟɜɢɞɧɨ, ɱɬɨ ɫɭɳɟɫɬɜɟɧɧɵɟ ɢɡɦɟɧɟɧɢɹ ɜ ɩɪɨɬɟɨɦɧɨɦ ɩɪɨɮɢɥɟ ɩɪɨɢɫɯɨɞɹɬ ɭɠɟ ɧɚ ɫɚɦɵɯ ɪɚɧɧɢɯ ɫɬɚɞɢɹɯ ɮɨɪɦɢɪɨɜɚɧɢɹ ɚɬɟɪɨɫɤɥɟɪɨɬɢɱɟɫɤɨɝɨ ɩɨɪɚɠɟɧɢɹ, ɬɨ ɟɫɬɶ ɩɪɢ ɠɢɪɨɜɨɣ ɢɧɮɢɥɶɬɪɚɰɢɢ. Ɇɚɤɪɨɫɤɨɩɢɱɟɫɤɢ ɧɚɱɚɥɶɧɵɟ ɩɨɪɚɠɟɧɢɹ ɩɪɟɞɫɬɚɜɥɹɸɬ ɫɨɛɨɣ ɭɱɚɫɬɤɢ ɫ ɝɥɚɞɤɨɣ ɠɟɥɬɨɜɚɬɨɣ ɩɨɜɟɪɯɧɨɫɬɶɸ, ɢɧɨɝɞɚ ɫ ɦɟɥɤɢɦɢ ɠɟɥɬɵɦɢ ɬɨɱɤɚɦɢ; ɦɢɤɪɨɫɤɨɩɢɱɟɫɤɢɟ ɢɡɦɟɧɟɧɢɹ ɩɪɢ ɷɬɨɦ ɦɢɧɢɦɚɥɶɧɵ: ɧɚɛɥɸɞɚɸɬɫɹ ɧɟɛɨɥɶɲɢɟ ɧɚɤɨɩɥɟɧɢɹ ɜɧɟɤɥɟɬɨɱɧɵɯ ɥɢɩɢɞɧɵɯ ɤɚɩɟɥɶ ɜ ɫɨɟɞɢɧɢɬɟɥɶɧɨ-ɬɤɚɧɧɨɦ ɦɚɬɪɢɤɫɟ. ɋɱɢɬɚɸɬ, ɱɬɨ ɜ ɭɱɚɫɬɤɚɯ ɧɚɱɚɥɶɧɵɯ ɩɨɪɚɠɟɧɢɣ, ɩɨɦɢɦɨ ɨɫɟɞɥɵɯ ɤɥɟɬɨɤ, ɨɬɦɟɱɚɟɬɫɹ ɧɟɫɤɨɥɶɤɨ ɭɜɟɥɢɱɟɧɧɨɟ ɩɨ ɫɪɚɜɧɟɧɢɸ ɫ ɧɟɩɨɪɚɠɟɧɧɨɣ ɢɧɬɢɦɨɣ ɤɨɥɢɱɟɫɬɜɨ ɦɨɧɨɧɭɤɥɟɚɪɧɵɯ ɤɥɟɬɨɤ; ɩɪɢ ɷɬɨɦ ɨɬɫɭɬɫɬɜɭɸɬ ɹɜɧɵɟ ɧɚɪɭɲɟɧɢɹ ɜ ɫɬɪɭɤɬɭɪɟ ɬɤɚɧɢ. ɉɪɢ ɷɬɨɦ ɩɪɨɬɟɨɦɧɵɣ ɩɪɨɮɢɥɶ ɬɤɚɧɢ ɭɠɟ ɫɭɳɟɫɬɜɟɧɧɨ ɢɡɦɟɧɟɧ. ɇɟɫɦɨɬɪɹ ɧɚ ɫɭɳɟɫɬɜɟɧɧɵɟ ɦɨɪɮɨɥɨɝɢɱɟɫɤɢɟ ɢɡɦɟɧɟɧɢɹ, ɩɪɨɢɫɯɨɞɹɳɢɟ ɩɪɢ ɩɪɨɝɪɟɫɫɢɪɨɜɚɧɢɢ ɚɬɟɪɨɫɤɥɟɪɨɡɚ (ɮɨɪɦɢɪɨɜɚɧɢɟ ɠɢɪɨɜɵɯ ɩɨɥɨɫ, ɥɢɩɨɮɢɛɪɨɡɧɵɯ ɢ ɮɢɛɪɨɡɧɵɯ ɛɥɹɲɟɤ – ɧɚɤɨɩɥɟɧɢɟ ɜɧɭɬɪɢɤɥɟɬɨɱɧɵɯ ɢ ɜɧɟɤɥɟɬɨɱɧɵɯ ɥɢɩɢɞɨɜ, ɪɚɡɪɚɫɬɚɧɢɟ ɫɨɟɞɢɧɢɬɟɥɶɧɨɬɤɚɧɧɨɝɨ ɦɚɬɪɢɤɫɚ, ɢɡɦɟɧɟɧɢɟ ɤɥɟɬɨɱɧɨɝɨ ɫɨɫɬɚɜɚ ɬɤɚɧɢ, ɮɨɪɦɢɪɨɜɚɧɢɟ ɜɨɡ- 83 ɜɵɲɚɸɳɢɯɫɹ ɩɨɪɚɠɟɧɢɣ), ɩɪɢɧɰɢɩɢɚɥɶɧɵɯ ɢɡɦɟɧɟɧɢɣ ɩɪɨɬɟɨɦɧɨɝɨ ɩɪɨɮɢɥɹ ɩɨ ɫɪɚɜɧɟɧɢɸ ɫ ɧɚɱɚɥɶɧɵɦɢ ɩɨɪɚɠɟɧɢɹɦɢ ɭɠɟ ɧɟ ɩɪɨɢɫɯɨɞɢɬ. ɋɱɢɬɚɟɬɫɹ, ɱɬɨ ɩɪɢ ɚɬɟɪɨɫɤɥɟɪɨɡɟ ɨɫɧɨɜɧɵɟ ɩɚɬɨɥɨɝɢɱɟɫɤɢɟ ɢɡɦɟɧɟɧɢɹ ɩɪɨɢɫɯɨɞɹɬ ɜ ɢɧɬɢɦɟ ɚɪɬɟɪɢɣ ɤɚɤ ɦɨɪɮɨɥɨɝɢɱɟɫɤɨɦ ɫɭɛɫɬɪɚɬɟ ɞɥɹ ɮɨɪɦɢɪɨɜɚɧɢɹ ɚɬɟɪɨɫɤɥɟɪɨɬɢɱɟɫɤɢɯ ɩɨɪɚɠɟɧɢɣ, ɚ ɜ ɦɟɞɢɚɥɶɧɨɦ ɫɥɨɟ ɧɚɛɥɸɞɚɸɬɫɹ ɜɬɨɪɢɱɧɵɟ ɢɡɦɟɧɟɧɢɹ. Ⱦɥɹ ɨɰɟɧɤɢ ɬɚɤɢɯ ɢɡɦɟɧɟɧɢɣ ɛɵɥɨ ɩɪɨɜɟɞɟɧɨ ɢɡɭɱɟɧɢɟ ɩɪɨɬɟɨɦɧɨɝɨ ɩɪɨɮɢɥɹ ɭɱɚɫɬɤɨɜ ɦɟɞɢɢ, ɩɨɞɥɟɠɚɳɢɯ ɩɨɞ ɧɟɢɡɦɟɧɟɧɧɨɣ ɢɧɬɢɦɨɣ ɢ ɩɨɞ ɥɢɩɨɮɢɛɪɨɡɧɨɣ ɛɥɹɲɤɨɣ (ɪɢɫ. 3.22). Ɉɱɟɜɢɞɧɨ, ɱɬɨ ɜ ɦɟɞɢɢ ɬɚɤɠɟ ɩɪɨɢɫɯɨɞɹɬ ɫɭɳɟɫɬɜɟɧɧɵɟ ɢɡɦɟɧɟɧɢɹ ɩɪɨɬɟɨɦɧɨɝɨ ɩɪɨɮɢɥɹ, ɚɫɫɨɰɢɢɪɨɜɚɧɧɵɟ ɫ ɧɚɥɢɱɢɟɦ ɚɬɟɪɨɫɤɥɟɪɨɬɢɱɟɫɤɨɝɨ ɩɨɪɚɠɟɧɢɹ. Ʉɥɸɱɟɜɵɟ ɪɚɡɥɢɱɢɹ ɛɟɥɤɨɜɵɯ ɩɹɬɟɧ, ɜɵɹɜɥɟɧɧɵɟ ɧɚ ɞɚɧɧɵɯ ɷɥɟɤɬɪɨɮɨɪɟɝɪɚɦɦɚɯ, ɩɪɢɜɟɞɟɧɵ ɜ ɬɚɛɥ. 3.2 (ɮɪɚɝɦɟɧɬɵ ɮɨɬɨ). ɇɚ ɪɢɫ. 3.21 ɩɪɟɞɫɬɚɜɥɟɧɨ ɮɨɬɨ ɷɥɟɤɬɪɨɮɨɪɟɝɪɚɦɦɵ ɷɤɫɬɪɚɤɬɚ ɛɟɥɤɨɜ ɢɡ ɦɟɞɢɢ, ɩɨɞɥɟɠɚɳɟɣ ɩɨɞ ɧɟɩɨɪɚɠɟɧɧɵɦ ɭɱɚɫɬɤɨɦ ɢɧɬɢɦɵ ɚɨɪɬɵ ɱɟɥɨɜɟɤɚ. ɋɬɪɟɥɤɚɦɢ ɭɤɚɡɚɧɵ ɛɟɥɤɨɜɵɟ ɩɹɬɧɚ ɜ ɨɛɥɚɫɬɢ ɛɟɥɤɨɜ ɦɚɫɫɨɣ ɦɟɧɟɟ 33 ɤȾɚ, ɞɥɹ ɤɨɬɨɪɵɯ ɧɚɛɥɸɞɚɸɬɫɹ ɧɚɢɛɨɥɟɟ ɜɵɪɚɠɟɧɧɵɟ ɤɨɥɢɱɟɫɬɜɟɧɧɵɟ ɢɡɦɟɧɟɧɢɹ ɩɪɢ ɚɧɚɥɢɡɟ ɭɱɚɫɬɤɨɜ ɦɟɞɢɢ, ɩɨɞɥɟɠɚɳɢɯ ɩɨɞ ɚɬɟɪɨɫɤɥɟɪɨɬɢɱɟɫɤɢɦɢ ɩɨɪɚɠɟɧɢɹɦɢ (ɥɢɩɨɮɢɛɪɨɡɧɵɦɢ ɢ ɮɢɛɪɨɡɧɵɦɢ ɛɥɹɲɤɚɦɢ). Ȼɵɥɚ ɩɪɟɞɩɪɢɧɹɬɚ ɩɨɩɵɬɤɚ ɢɞɟɧɬɢɮɢɤɚɰɢɢ ɞɚɧɧɵɯ ɛɟɥɤɨɜ ɫ ɢɫɩɨɥɶɡɨɜɚɧɢɟɦ ɬɟɯɧɨɥɨɝɢɢ MALDI-TOF ɦɚɫɫ-ɫɩɟɤɬɪɨɦɟɬɪɢɢ. Ɋɟɡɭɥɶɬɚɬɵ ɚɧɚɥɢɡɚ ɩɪɟɞɫɬɚɜɥɟɧɵ ɜ ɬɚɛɥ. 3.3. ɗɬɢ ɧɢɡɤɨɦɨɥɟɤɭɥɹɪɧɵɟ ɛɟɥɤɢ ɨɤɚɡɚɥɢɫɶ ɮɪɚɝɦɟɧɬɚɦɢ ɢɡɨɮɨɪɦɵ 1 ɚɧɧɟɤɫɢɧɚ-2, ɚɥɶɮɚ-ȼ-ɤɪɢɫɬɚɥɥɢɧɚ, r-ras ɨɧɤɨɝɟɧɚ, ɛɟɥɤɚ ɬɟɩɥɨɜɨɝɨ ɲɨɤɚ ɛɟɬɚ-1, ɛɟɬɚɝɥɨɛɢɧɚ, ɬɪɚɧɫɝɟɥɢɧɚ ɢ ɟɝɨ ɢɡɨɮɨɪɦ, ɚ ɬɚɤɠɟ ɩɟɪɨɤɫɢɪɟɞɨɤɫɢɧɚ-1. ɋɥɟɞɭɟɬ ɨɬɦɟɬɢɬɶ, ɱɬɨ ɞɚɧɧɵɣ ɚɧɚɥɢɡ ɧɨɫɢɥ ɜɟɫɶɦɚ ɨɝɪɚɧɢɱɟɧɧɵɣ ɯɚɪɚɤɬɟɪ. ɂɡ-ɡɚ ɫɥɨɠɧɨɫɬɢ ɩɪɨɰɟɞɭɪɵ ɢɞɟɧɬɢɮɢɤɚɰɢɢ ɧɚ ɞɚɧɧɨɦ ɷɬɚɩɟ ɢɫɫɥɟɞɨɜɚɧɢɹ ɧɟ ɛɵɥɢ ɜɤɥɸɱɟɧɵ ɛɟɥɤɢ ɫ ɦɨɥɟɤɭɥɹɪɧɨɣ ɦɚɫɫɨɣ ɛɨɥɟɟ 40 ɤȾɚ, ɯɨɬɹ ɢɡ ɪɟɡɭɥɶɬɚɬɨɜ 2D ɷɥɟɤɬɪɨɮɨɪɟɡɚ, ɩɪɟɞɫɬɚɜɥɟɧɧɵɯ 84 ɧɚ ɪɢɫ. 3.19–3.22, ɨɱɟɜɢɞɧɨ, ɱɬɨ ɜ ɷɬɨɦ ɞɢɚɩɚɡɨɧɟ ɦɨɥɟɤɭɥɹɪɧɵɯ ɦɚɫɫ ɩɪɢ ɪɚɡɜɢɬɢɢ ɚɬɟɪɨɫɤɥɟɪɨɬɢɱɟɫɤɢɯ ɩɨɪɚɠɟɧɢɣ ɬɚɤɠɟ ɩɪɨɢɫɯɨɞɹɬ ɫɭɳɟɫɬɜɟɧɧɵɟ ɢɡɦɟɧɟɧɢɹ ɩɪɨɬɟɨɦɧɨɝɨ ɩɪɨɮɢɥɹ ɤɚɤ ɜ ɢɧɬɢɦɚɥɶɧɨɦ, ɬɚɤ ɢ ɦɟɞɢɚɥɶɧɨɦ ɫɥɨɟ ɚɨɪɬɵ. Ɍɚɛɥɢɰɚ 3.2. Ɏɪɚɝɦɟɧɬɵ ɞɜɭɦɟɪɧɵɯ ɷɥɟɤɬɪɨɮɨɪɟɝɪɚɦɦ ɛɟɥɤɨɜ ɦɟɞɢɢ ɚɨɪɬɵ ɱɟɥɨɜɟɤɚ ɍɱɚɫɬɨɤ ɩɨɞ ɧɟɩɨɪɚɠɟɧɧɨɣ ɢɧɬɢɦɨɣ ɍɱɚɫɬɨɤ ɩɨɞ ɥɢɩɨɮɢɛɪɨɡɧɨɣ ɛɥɹɲɤɨɣ Ɋɚɡɥɢɱɢɹ ɂɫɱɟɡɧɨɜɟɧɢɟ ɛɟɥɤɨɜɨɝɨ ɩɹɬɧɚ 29 ɤȾɚ ɉɨɹɜɥɟɧɢɟ ɩɹɬɧɚ 26 ɤȾɚ, ɢɫɱɟɡɧɨɜɟɧɢɹ ɩɹɬɧɚ 27 ɤȾɚ Ʉɨɥɢɱɟɫɬɜɟɧɧɵɟ ɢɡɦɟɧɟɧɢɹ ɛɟɥɤɨɜɨɝɨ ɩɹɬɧɚ 17 ɤȾɚ ɂɫɱɟɡɧɨɜɟɧɢɟ ɛɟɥɤɨɜɨɝɨ ɩɹɬɧɚ 19 ɤȾɚ, ɤɨɥɢɱɟɫɬɜɟɧɧɵɟ ɢɡɦɟɧɟɧɢɹ ɞɪɭɝɢɯ ɛɟɥɤɨɜɵɯ ɩɹɬɟɧ Ʉɨɥɢɱɟɫɬɜɟɧɧɵɟ ɢɡɦɟɧɟɧɢɹ ɛɟɥɤɨɜɵɯ ɩɹɬɟɧ 24 ɤȾɚ 85 Ɍɚɛɥɢɰɚ 3.3. Ɋɟɡɭɥɶɬɚɬɵ ɢɞɟɧɬɢɮɢɤɚɰɢɢ ɩɹɬɟɧ ɛɟɥɤɨɜ ɢɡ 2D ɷɥɟɤɬɪɨɮɨɪɟɝɪɚɦɦ ɛɟɥɤɨɜ ɦɟɞɢɢ ɚɨɪɬɵ ɱɟɥɨɜɟɤɚ ʋ Ȼɟɥɨɤ ɇɨɦɟɪ ɜ NCBI protein ȼɟɪɨɹɬɧɨɫɬɧɵɣ % ɤɨɷɮɮɢɰɢɟɧɬ ɞɨɫɩɟɪɟɬɨɜɟɪɧɨɫɬɢ / ɤɨɥɢɤɪɵɱɟɫɬɜɨ ɜɵɹɜɥɟɧɬɢɹ ɧɵɯ ɦɚɫɫ ɩɟɩɬɢɞɨɜ Mw/pI ɷɤɫɩ. Mw/pI ɬɟɨɪ. 6 Ⱥɧɧɟɤɫɢɧ-2, ɢɡɨɮɨɪ50845388 ɦɚ 1 (ɮɪɚɝɦɟɧɬ) Ⱥɥɶɮɚ-ȼ-ɤɪɢɫɬɚɥɥɢɧ 4503057 r-ras ɨɧɤɨɝɟɧ 5454028 Ȼɟɥɨɤ ɬɟɩɥɨɜɨɝɨ 4504517 ɲɨɤɚ ɛɟɬɚ-1 Ȼɟɥɨɤ ɬɟɩɥɨɜɨɝɨ 4504517 ɲɨɤɚ ɛɟɬɚ-1 ɐɟɩɶ Ⱥ ɝɟɦɨɝɥɨɛɢɧɚ 61679690 7 Ȼɟɬɚ ɝɥɨɛɢɧ 71727231 117/7 60 16,0/7,80 16,0/7,86 8 Ɍɪɚɧɫɝɟɥɢɧ 48255905 89/10 50 22,6/8,87 9 Ɍɪɚɧɫɝɟɥɢɧ 48255905 206/22 83 22,6/8,87 10 Ɍɪɚɧɫɝɟɥɢɧ 48255905 145/10 53 22,6/8,87 122/10, 53/5 52, 27 22,6/8,87 147/12 47 22,6/8,87 1 2 3 4 5 ɋɦɟɫɶ ɬɪɚɧɫɝɟɥɢɧɚ ɢ 48255905, 11 ɩɟɪɨɤɫɢɪɟɞɨɤɫɢɧɚ-1 55959887 74/11 35 35,0/7,25 40,4/8,53 62/5 117/8 23 45 19,5/7,30 20,1/6,76 22,5/6,50 23,5/6,44 97/10 52 23,0/5,60 22,8/5,98 97/10 25 23,0/5,80 22,8/5,98 68/8 64 15,5/8,30 15,1/8,72 12 Ɍɪɚɧɫɝɟɥɢɧ 48255905 13 Ɍɪɚɧɫɝɟɥɢɧ 48255905 106/8 37 22,6/8,87 14 Ɍɪɚɧɫɝɟɥɢɧ 48255905 142/10 45 22,6/8,87 15 Ɍɪɚɧɫɝɟɥɢɧ 48255905 172/21 73 22,6/8,87 16 Ɍɪɚɧɫɝɟɥɢɧ 48255905 Ɍɪɚɧɫɝɟɥɢɧ, ɢɡɨɮɨɪ17 119587704 ɦɚ CRA_c 18 Ⱥɥɶɮɚ-ȼ-ɤɪɢɫɬɚɥɥɢɧ 4503057 143/17 64 22,6/8,87 55/6 33 23,7/8,54 62/5 26 20,1/6,76 19 Ɍɪɚɧɫɝɟɥɢɧ ɜɚɪɢɚɧɬ 62897565 67/6 23 20,9/8,69 20 Ɍɪɚɧɫɝɟɥɢɧ ɜɚɪɢɚɧɬ 62897565 54/5 28 20,9/8,69 ɉɪɢɦɟɱɚɧɢɟ: ɩɪɢɜɟɞɟɧɵ ɪɟɡɭɥɶɬɚɬɵ ɤɨɦɩɶɸɬɟɪɧɨɝɨ ɩɨɢɫɤɚ ɩɨ ɛɚɡɚɦ ɞɚɧɧɵɯ ɨ ɫɟɤɜɟɧɢɪɨɜɚɧɧɵɯ ɩɨɫɥɟɞɨɜɚɬɟɥɶɧɨɫɬɹɯ (NCBI, www.ncbi.nlm.nih.gov) - ɩɪɨɰɟɧɬ ɫɨɜɩɚɞɟɧɢɹ ɜɵɹɜɥɟɧɧɵɯ ɦɚɫɫ ɬɪɢɩɬɢɱɟɫɤɢɯ ɩɟɩɬɢɞɨɜ ɫ ɚɦɢɧɨɤɢɫɥɨɬɧɨɣ ɩɨɫɥɟɞɨɜɚɬɟɥɶɧɨɫɬɶɸ ɫɨɨɬɜɟɬɫɬɜɭɸɳɟɝɨ ɛɟɥɤɚ 86 Ɋɢɫ. 3.19. 2D ɷɥɟɤɬɪɨɮɨɪɟɡ ɷɤɫɬɪɚɤɬɨɜ ɛɟɥɤɨɜ ɢɡ ɢɧɬɢɦɵ ɚɨɪɬɵ ɱɟɥɨɜɟɤɚ. ɋɥɟɜɚ – ɧɟɩɨɪɚɠɟɧɧɚɹ ɢɧɬɢɦɚ ɚɨɪɬɵ, ɫɩɪɚɜɚ – ɥɢɩɨɮɢɛɪɨɡɧɚɹ ɛɥɹɲɤɚ. Ɉɤɪɚɫɤɚ ɫɟɪɟɛɪɨɦ Ɋɢɫ. 3.20. 2D ɷɥɟɤɬɪɨɮɨɪɟɡ ɷɤɫɬɪɚɤɬɨɜ ɛɟɥɤɨɜ ɢɡ ɢɧɬɢɦɵ ɚɨɪɬɵ ɱɟɥɨɜɟɤɚ. ȼɜɟɪɯɭ ɫɥɟɜɚ – ɧɟɩɨɪɚɠɟɧɧɚɹ ɢɧɬɢɦɚ ɚɨɪɬɵ, ɜɜɟɪɯɭ ɩɨɫɟɪɟɞɢɧɟ – ɠɢɪɨɜɚɹ ɢɧɮɢɥɶɬɪɚɰɢɹ (ɧɚɱɚɥɶɧɵɟ ɩɨɪɚɠɟɧɢɹ), ɜɜɟɪɯɭ ɫɩɪɚɜɚ – ɠɢɪɨɜɚɹ ɩɨɥɨɫɚ, ɜɧɢɡɭ ɫɥɟɜɚ - ɥɢɩɨɮɢɛɪɨɡɧɚɹ ɛɥɹɲɤɚ, ɜɧɢɡɭ ɫɩɪɚɜɚ – ɮɢɛɪɨɡɧɚɹ ɛɥɹɲɤɚ. Ɉɤɪɚɫɤɚ ɫɟɪɟɛɪɨɦ 87 Ɋɢɫ. 3.21. 2D ɷɥɟɤɬɪɨɮɨɪɟɡ ɷɤɫɬɪɚɤɬɨɜ ɛɟɥɤɨɜ ɢɡ ɭɱɚɫɬɤɚ ɦɟɞɢɢ ɚɨɪɬɵ ɱɟɥɨɜɟɤɚ, ɩɨɞɥɟɠɚɳɟɝɨ ɩɨɞ ɧɟɩɨɪɚɠɟɧɧɵɦ ɭɱɚɫɬɤɨɦ ɢɧɬɢɦɵ (ɫɥɟɜɚ) ɢ ɩɨɞ ɥɢɩɨɮɢɛɪɨɡɧɨɣ ɛɥɹɲɤɨɣ (ɫɩɪɚɜɚ). Ɉɤɪɚɫɤɚ ɫɟɪɟɛɪɨɦ Ɋɢɫ. 3.22. 2D ɷɥɟɤɬɪɨɮɨɪɟɡ ɷɤɫɬɪɚɤɬɚ ɛɟɥɤɨɜ ɢɡ ɭɱɚɫɬɤɚ ɦɟɞɢɢ ɚɨɪɬɵ ɱɟɥɨɜɟɤɚ, ɩɨɞɥɟɠɚɳɟɝɨ ɩɨɞ ɧɟɩɨɪɚɠɟɧɧɵɦ ɭɱɚɫɬɤɨɦ ɢɧɬɢɦɵ. ɋɬɪɟɥɤɚɦɢ ɭɤɚɡɚɧɵ ɩɹɬɧɚ, ɢɞɟɧɬɢɮɢɰɢɪɨɜɚɧɧɵɟ ɫ ɩɨɦɨɳɶɸ MALDI-TOF ɦɚɫɫ-ɫɩɟɤɬɪɨɦɟɬɪɢɢ. Ɉɤɪɚɫɤɚ ɫɟɪɟɛɪɨɦ 88 4. ɈȻɋɍɀȾȿɇɂȿ ɊȿɁɍɅɖɌȺɌɈȼ 4.1. Ɋɟɚɤɰɢɹ ɨɫɬɟɨɛɥɚɫɬɨɜ ɧɚ ɉɌȽ Ɉɞɧɚ ɢɡ ɡɚɞɚɱ ɧɚɲɟɝɨ ɢɫɫɥɟɞɨɜɚɧɢɹ – ɫɨɡɞɚɧɢɟ ɛɚɡɨɜɨɣ, ɷɬɚɥɨɧɧɨɣ ɦɨɞɟɥɢ ɞɥɹ ɨɰɟɧɤɢ ɪɚɡɥɢɱɧɵɯ ɦɚɧɢɩɭɥɹɰɢɣ ɫ ȽɋɄ ɫ ɩɪɢɦɟɧɟɧɢɟɦ ɦɟɬɨɞɨɥɨɝɢɢ ɩɪɨɬɟɨɦɢɤɢ. ɇɚ ɧɚɱɚɥɶɧɨɦ ɷɬɚɩɟ ɪɚɛɨɬɵ ɛɵɥɢ ɢɫɩɨɥɶɡɨɜɚɧɵ ɨɫɬɟɨɛɥɚɫɬɵ ɞɥɹ ɪɚɡɜɢɬɢɹ ɦɟɬɨɞɚ ɢ ɩɪɨɜɟɪɤɢ ɧɟɤɨɬɨɪɵɯ ɝɢɩɨɬɟɡ, ɚ ɬɚɤɠɟ ɤɨɧɬɪɨɥɹ ɫɬɢɦɭɥɢɪɨɜɚɧɢɹ ɤɥɟɬɨɤ ɡɚ ɫɱɟɬ ɜɧɟɲɧɢɯ ɮɚɤɬɨɪɨɜ. ɗɬɨ ɹɜɥɹɟɬɫɹ ɩɟɪɟɯɨɞɧɵɦ ɷɬɚɩɨɦ ɤ ɢɫɫɥɟɞɨɜɚɧɢɸ ɮɚɤɬɨɪɨɜ, ɪɟɝɭɥɢɪɭɸɳɢɯ ȽɋɄ, ɜ ɬɨɦ ɱɢɫɥɟ ɤ ɩɨɧɢɦɚɧɢɸ ɩɪɢɪɨɞɵ ɢɯ ɟɫɬɟɫɬɜɟɧɧɨɝɨ ɫɨɫɬɨɹɧɢɹ. ɗɤɫɩɟɪɢɦɟɧɬ ɫ ɢɫɩɨɥɶɡɨɜɚɧɢɟɦ ɉɌȽ ɩɪɨɞɟɦɨɧɫɬɪɢɪɨɜɚɥ, ɱɬɨ 2D – ɷɮɮɟɤɬɢɜɧɵɣ ɢɧɫɬɪɭɦɟɧɬ ɞɥɹ ɧɟɪɚɡɪɭɲɚɸɳɟɝɨ ɦɨɧɢɬɨɪɢɧɝɚ ɢɡɦɟɧɟɧɢɣ ɛɟɥɤɨɜ ɜ ɨɬɜɟɬ ɧɚ ɝɨɪɦɨɧɚɥɶɧɭɸ ɫɬɢɦɭɥɹɰɢɸ. ɂɡ ɩɪɟɞɜɚɪɢɬɟɥɶɧɵɯ ɪɟɡɭɥɶɬɚɬɨɜ ɜɢɞɧɨ, ɱɬɨ ɉɌȽ (1-34) ɫɬɢɦɭɥɢɪɭɟɬ ɜɵɠɢɜɚɧɢɟ ɧɚɯɨɞɹɳɢɯɫɹ ɜ ɫɬɚɞɢɢ ɩɨɤɨɹ (ɥɢɲɟɧɧɵɯ ɩɢɬɚɧɢɹ) ɨɫɬɟɨɛɥɚɫɬɨɜ. ɂɯ ɨɬɦɢɪɚɧɢɟ, ɚɫɫɨɰɢɢɪɨɜɚɧɧɨɟ ɫ ɮɚɤɬɨɪɨɦ ɬɪɚɧɫɤɪɢɩɰɢɢ 1, ɫɧɢɠɚɟɬɫɹ ɜ 4 ɪɚɡɚ ɩɨɫɥɟ ɨɛɪɚɛɨɬɤɢ ɉɌȽ ɩɨ ɫɪɚɜɧɟɧɢɸ ɫ ɤɨɧɬɪɨɥɟɦ. ȼ ɥɢɬɟɪɚɬɭɪɟ ɢɦɟɸɬɫɹ ɫɨɨɛɳɟɧɢɹ ɨ ɩɪɹɦɨɦ ɜɥɢɹɧɢɢ ɨɫɬɟɨɛɥɚɫɬɩɨɞɨɛɧɵɯ ɤɥɟɬɨɱɧɵɯ ɥɢɧɢɣ ɧɚ ɝɟɦɚɬɨɩɨɷɡ in vitro. Ɋɹɞ ɚɜɬɨɪɨɜ ɩɨɥɚɝɚɟɬ, ɱɬɨ ɤɥɟɬɨɱɧɵɟ ɥɢɧɢɢ ɨɫɬɟɨɫɚɪɤɨɦɵ ɧɟ ɩɨɞɞɟɪɠɢɜɚɸɬ ɤɚɤ ɩɪɨɝɟɧɢɬɨɪɧɭɸ ɚɤɬɢɜɧɨɫɬɶ in vitro, ɬɚɤ ɢ ɩɟɪɜɢɱɧɵɟ (primary) ɫɬɜɨɥɨɜɵɟ ɤɥɟɬɤɢ [14,15]. ɉɪɟɞɩɨɥɚɝɚɟɬɫɹ, ɱɬɨ ɤɥɟɬɨɱɧɵɟ ɥɢɧɢɢ ɨɫɬɟɨɫɚɪɤɨɦɵ ɱɟɥɨɜɟɤɚ ɧɟ ɫɩɨɫɨɛɧɵ ɩɨɞɞɟɪɠɢɜɚɬɶ ɜɵɠɢɜɚɧɢɟ CD34+ ɤɥɟɬɨɤ ɤɨɫɬɧɨɝɨ ɦɨɡɝɚ ɢɡɡɚ ɜɵɫɨɤɨɝɨ ɫɨɞɟɪɠɚɧɢɹ ɬɪɚɧɫɮɨɪɦɢɪɭɸɳɟɝɨ ɮɚɤɬɨɪɚ ɪɨɫɬɚ (TGF), ɩɪɨɢɡɜɨɞɢɦɨɝɨ ɤɥɟɬɤɚɦɢ ɷɬɢɯ ɥɢɧɢɣ [85]. ɉɪɢ ɢɫɩɨɥɶɡɨɜɚɧɢɢ ɤɥɟɬɨɱɧɨɣ ɥɢɧɢɢ CAL72 ɨɫɬɟɨɫɚɪɤɨɦɵ ɩɨɤɚɡɚɧɨ, ɱɬɨ ɨɝɪɚɧɢɱɟɧɧɨɟ ɪɚɡɦɧɨ- 89 ɠɟɧɢɟ ɝɟɦɨɩɨɷɬɢɱɟɫɤɢɯ ɩɪɨɝɟɧɢɬɨɪɧɵɯ ɤɥɟɬɨɤ, ɚɧɚɥɨɝɢɱɧɵɯ ɩɟɪɜɢɱɧɵɦ ɨɫɬɟɨɛɥɚɫɬɚɦ ɱɟɥɨɜɟɤɚ, ɜɩɨɥɧɟ ɜɨɡɦɨɠɧɨ [71]. Ɉɞɧɚɤɨ ɜ ɷɬɢɯ ɨɩɵɬɚɯ ɛɵɥɢ ɢɫɩɨɥɶɡɨɜɚɧɵ CD34+ ɤɥɟɬɤɢ ɢɡ ɩɭɩɨɜɢɧɧɨɣ ɤɪɨɜɢ, ɱɬɨ ɡɚɬɪɭɞɧɹɟɬ ɢɧɬɟɪɩɪɟɬɚɰɢɸ ɩɨɜɟɞɟɧɢɹ ɨɫɬɟɨɛɥɚɫɬɨɜ ɩɨ ɨɬɧɨɲɟɧɢɸ ɤ ɤɥɟɬɤɚɦ ɤɨɫɬɧɨɝɨ ɦɨɡɝɚ [71]. Ɉɬɦɟɬɢɦ ɬɚɤɠɟ, ɱɬɨ ɨɫɬɟɨɫɚɪɤɨɦɚ ɤɥɟɬɨɱɧɨɣ ɥɢɧɢɢ U2-OS ɩɨɞɞɟɪɠɢɜɚɟɬ ɩɪɨɥɢɮɟɪɚɰɢɸ ɪɚɧɧɢɯ ɤɥɟɬɨɤ ɤɨɫɬɧɨɝɨ ɦɨɡɝɚ [73]. ȼɡɹɬɵɟ ɜɦɟɫɬɟ, ɷɬɢ ɢɫɫɥɟɞɨɜɚɧɢɹ ɭɤɚɡɵɜɚɸɬ ɧɚ ɬɨ, ɱɬɨ, ɯɨɬɹ ɨɫɬɟɨɫɚɪɤɨɦɚ ɢ ɬɪɚɧɫɮɨɪɦɢɪɨɜɚɧɧɵɟ ɤɥɟɬɨɱɧɵɟ ɥɢɧɢɢ ɨɫɬɟɨɛɥɚɫɬɨɜ ɦɨɝɭɬ ɩɨɞɞɟɪɠɢɜɚɬɶ ɩɪɨɥɢɮɟɪɚɰɢɸ, ɢɯ ɫɩɨɫɨɛɧɨɫɬɶ ɩɨɞɞɟɪɠɢɜɚɬɶ ɪɚɧɧɢɟ ȽɋɄ ɯɨɬɶ ɢ ɜɨɡɦɨɠɧɚ, ɧɨ ɜɟɫɶɦɚ ɨɝɪɚɧɢɱɟɧɧɚ. ɋɬɜɨɥɨɜɨɫɬɶ – ɤɥɸɱɟɜɨɟ ɫɜɨɣɫɬɜɨ ɜɫɟɯ ɋɄ. Ɍɚɤ ɩɪɢɧɹɬɨ ɧɚɡɵɜɚɬɶ ɢɯ ɫɩɨɫɨɛɧɨɫɬɶ ɤ ɫɚɦɨɨɛɧɨɜɥɟɧɢɸ ɢ ɜɨɡɦɨɠɧɨɫɬɶ ɫɨɡɞɚɜɚɬɶ ɞɢɮɮɟɪɟɧɰɢɪɭɸɳɟɟɫɹ ɩɨɬɨɦɫɬɜɨ. Ʉɚɤɢɟ ɮɚɤɬɨɪɵ ɭɩɪɚɜɥɹɸɬ ɷɬɨɣ ɫɩɨɫɨɛɧɨɫɬɶɸ? Ɉɞɧɚ ɢɡ ɝɢɩɨɬɟɡ, ɨɬɜɟɱɚɸɳɢɯ ɧɚ ɷɬɨɬ ɜɨɩɪɨɫ, ɭɤɚɡɵɜɚɟɬ ɧɚ ɪɨɥɶ ɦɢɤɪɨɨɤɪɭɠɟɧɢɹ ɋɄ [9, 84,107], ɩɨɥɭɱɢɜɲɟɝɨ ɧɚɡɜɚɧɢɟ ɧɢɲɢ ɋɄ. ȼ ɷɬɨɣ ɫɜɹɡɢ ɜ ɧɚɲɟɣ ɪɚɛɨɬɟ ɢɫɩɨɥɶɡɨɜɚɧɵ ɨɫɬɟɨɛɥɚɫɬɵ, ɹɜɥɹɸɳɢɟɫɹ ɜɚɠɧɵɦɢ ɤɨɦɩɨɧɟɧɬɚɦɢ ɧɢɲɢ. Ɉɫɬɟɨɛɥɚɫɬɵ ɨɬɧɨɫɢɬɟɥɶɧɨ ɩɪɨɫɬɨ ɝɨɬɨɜɹɬɫɹ ɞɥɹ ɢɫɫɥɟɞɨɜɚɬɟɥɶɫɤɢɯ ɰɟɥɟɣ ɢ ɦɨɝɭɬ ɩɨɫɥɭɠɢɬɶ ɦɚɬɟɪɢɚɥɨɦ ɞɥɹ ɫɨɡɞɚɧɢɹ ɩɪɨɬɨɤɨɥɚ ɩɪɨɬɟɨɦɧɨɝɨ ɚɧɚɥɢɡɚ. Ɉɫɬɟɨɛɥɚɫɬɵ ɞɚɸɬ ɜɨɡɦɨɠɧɨɫɬɶ ɢɡɭɱɟɧɢɹ ɫɬɢɦɭɥɢɪɨɜɚɧɢɹ ɤɥɟɬɨɤ ɡɚ ɫɱɟɬ ɜɧɟɲɧɢɯ ɮɚɤɬɨɪɨɜ, ɚ ɨɩɵɬɵ ɫ ɧɢɦɢ ɹɜɥɹɸɬɫɹ ɩɟɪɟɯɨɞɧɵɦ ɷɬɚɩɨɦ ɤ ɢɫɫɥɟɞɨɜɚɧɢɸ ɮɚɤɬɨɪɨɜ, ɪɟɝɭɥɢɪɭɸɳɢɯ ȽɋɄ. ɇɚɩɪɢɦɟɪ, ɦɨɠɧɨ ɨɠɢɞɚɬɶ, ɱɬɨ Jagged1 (Jag1), ɜɵɞɟɥɹɟɦɵɣ ɨɫɬɟɨɛɥɚɫɬɚɦɢ ɜ ɨɬɜɟɬ ɧɚ ɨɛɪɚɛɨɬɤɭ ɉɌȽ, ɜɥɢɹɟɬ ɧɚ ȽɋɄ ɩɨ ɫɢɝɧɚɥɶɧɨɦɭ ɩɭɬɢ ɱɟɪɟɡ ɪɟɰɟɩɬɨɪ Notch-1 [28, 73]. ɉɨɢɫɤ ɮɚɤɬɨɪɨɜ, ɤɨɬɨɪɵɟ ɫɩɨɫɨɛɫɬɜɭɸɬ ɪɚɡɦɧɨɠɟɧɢɸ ȽɋɄ ɜ ɤɭɥɶɬɭɪɟ, ɩɪɨɜɨɞɢɥɫɹ ɢ ɫ ɢɫɩɨɥɶɡɨɜɚɧɢɟɦ ɢɦɦɨɛɢɥɢɡɨɜɚɧɧɨɝɨ Jag1 [96]. ɉɪɢ ɷɬɨɦ Jag1-ɫɮɟɪɵ ɢɦɢɬɢɪɨɜɚɥɢ ɞɟɣɫɬɜɢɟ ɨɫ90 ɬɟɨɛɥɚɫɬɨɜ ɜ ɧɢɲɟ ȽɋɄ. Ɉɩɪɟɞɟɥɢɜ ɧɢɲɭ ɤɚɤ ɞɟɬɟɪɦɢɧɚɧɬɭ ɜ ɪɟɝɭɥɹɰɢɢ ȽɋɄ, ɪɨɥɶ ɜɧɭɬɪɟɧɧɢɯ ɫɢɝɧɚɥɨɜ ɩɪɟɞɫɬɚɜɥɹɟɬɫɹ ɫ ɧɨɜɨɣ ɬɨɱɤɢ ɡɪɟɧɢɹ – ɧɟ ɬɨɥɶɤɨ ɤɚɤ ɪɟɝɭɥɢɪɭɸɳɢɯ ɫɚɦɢ ɩɨ ɫɟɛɟ, ɧɨ ɢ ɜɨ ɜɡɚɢɦɨɞɟɣɫɬɜɢɢ ɫ ɞɪɭɝɢɦɢ ɢɧɫɬɪɭɦɟɧɬɚɦɢ (ɧɚɩɪɢɦɟɪ, ɰɢɬɨɤɢɧɚɦɢ) ɞɥɹ ɤɨɥɥɟɤɬɢɜɧɨɝɨ ɜɥɢɹɧɢɹ ɧɢɲɢ ɧɚ ɮɭɧɤɰɢɨɧɢɪɨɜɚɧɢɟ ɋɄ. ɉɪɟɞɩɨɥɚɝɚɟɦɵɟ ɷɮɮɟɤɬɵ ɦɢɤɪɨɫɮɟɪ ɫ Jag1 ɢ ɢɯ ɚɧɚɥɨɝɨɜ in vivo ɜ ɮɨɪɦɟ ɨɫɬɟɨɛɥɚɫɬɨɜ ɧɚ ȽɋɄ ɹɜɥɹɸɬɫɹ ɬɨɣ ɫɬɚɪɬɨɜɨɣ ɬɨɱɤɨɣ, ɢɫɯɨɞɹ ɢɡ ɤɨɬɨɪɨɣ ɩɪɨɬɟɨɦɢɤɚ ɞɚɟɬ ɜɨɡɦɨɠɧɨɫɬɶ ɢɫɫɥɟɞɨɜɚɬɶ ɪɨɥɶ ɨɫɬɟɨɛɥɚɫɬɨɜ ɜ ɩɪɨɥɢɮɟɪɚɰɢɢ ȽɋɄ. Ʉɪɨɦɟ ɬɨɝɨ, ɧɚɦɢ ɞɨɫɬɢɝɧɭɬɚ ɨɩɬɢɦɢɡɚɰɢɹ ɢɫɩɨɥɶɡɨɜɚɧɢɹ ɞɨɫɬɭɩɧɵɯ ɬɟɯɧɨɥɨɝɢɣ, ɤɨɦɛɢɧɢɪɨɜɚɧɢɟ ɤɨɬɨɪɵɯ ɩɨɡɜɨɥɢɥɨ ɩɨɥɭɱɢɬɶ ɭɥɭɱɲɟɧɧɵɟ ɪɟɡɭɥɶɬɚɬɵ ɩɪɨɬɟɨɦɧɨɝɨ ɚɧɚɥɢɡɚ. Ƚɥɚɜɧɨɣ ɨɫɨɛɟɧɧɨɫɬɶɸ ɩɪɟɞɥɚɝɚɟɦɨɝɨ ɦɟɬɨɞɢɱɟɫɤɨɝɨ ɩɨɞɯɨɞɚ ɹɜɥɹɟɬɫɹ ɬɪɟɯɫɬɭɩɟɧɱɚɬɚɹ ɩɪɨɰɟɞɭɪɚ ɮɪɚɤɰɢɨɧɢɪɨɜɚɧɢɹ ɛɢɨɥɨɝɢɱɟɫɤɨɝɨ ɦɚɬɟɪɢɚɥɚ, ɜɟɞɭɳɚɹ ɤ ɩɨɜɵɲɟɧɢɸ ɷɮɮɟɤɬɢɜɧɨɫɬɢ ɪɚɡɞɟɥɟɧɢɹ ɛɟɥɤɨɜ ɦɟɬɨɞɨɦ ɞɜɭɦɟɪɧɨɝɨ ɝɟɥɶ-ɷɥɟɤɬɪɨɮɨɪɟɡɚ ɧɚ ɩɨɥɢɚɤɪɢɥɚɦɢɞɟ. Ɍɚɤɢɦ ɨɛɪɚɡɨɦ, ɦɵ ɚɤɰɟɧɬɢɪɭɟɦ ɜɧɢɦɚɧɢɟ ɧɚ ɜɚɠɧɨɫɬɢ ɩɨɞɝɨɬɨɜɤɢ ɨɛɪɚɡɰɚ (ɤɥɟɬɨɱɧɨɝɨ ɫɨɞɟɪɠɢɦɨɝɨ), ɜɤɥɸɱɚɹ ɭɥɶɬɪɚɡɜɭɤɨɜɨɟ ɪɚɡɪɭɲɟɧɢɟ ɦɟɦɛɪɚɧ ɢ ɪɚɡɞɟɥɟɧɢɟ ɫɭɛɤɥɟɬɨɱɧɵɯ ɱɚɫɬɢɰ, ɩɨɡɜɨɥɹɸɳɟɟ ɜ ɞɚɥɶɧɟɣɲɟɦ ɩɪɨɜɨɞɢɬɶ ɚɧɚɥɢɡ ɛɟɥɤɨɜ, ɩɪɢɫɭɬɫɬɜɭɸɳɢɯ ɜ ɧɢɡɤɢɯ ɤɨɧɰɟɧɬɪɚɰɢɹɯ. ȼ ɱɚɫɬɧɨɫɬɢ, ɞɢɮɮɟɪɟɧɰɢɚɥɶɧɨɟ ɷɤɫɬɪɚɝɢɪɨɜɚɧɢɟ ɛɟɥɤɨɜ ɨɫɭɳɟɫɬɜɥɹɟɬɫɹ ɫ ɩɨɦɨɳɶɸ ɤɨɦɦɟɪɱɟɫɤɢ ɞɨɫɬɭɩɧɨɝɨ ɧɚɛɨɪɚ ɪɟɚɝɟɧɬɨɜ ProteoExtract® Subcellular Proteome Extraction Kit (S-PEK, Calbiochem, Germany). ɗɬɨɬ ɧɚɛɨɪ ɫɨɞɟɪɠɢɬ ɷɤɫɬɪɚɤɰɢɨɧɧɵɟ ɛɭɮɟɪɧɵɟ ɪɚɫɬɜɨɪɵ, ɩɪɢɝɨɬɨɜɥɟɧɧɵɟ ɫ ɢɫɩɨɥɶɡɨɜɚɧɢɟɦ ɫɨɟɞɢɧɟɧɢɣ ɜɵɫɨɤɨɣ ɱɢɫɬɨɬɵ, ɫɦɟɫɶ ɩɪɨɬɟɚɡ ɢ ɧɭɤɥɟɚɡɭ, ɭɫɬɪɚɧɹɸɳɭɸ ɧɭɤɥɟɢɧɨɜɵɟ ɤɢɫɥɨɬɵ. Ɉɞɧɢɦ ɢɡ ɩɪɟɢɦɭɳɟɫɬɜ SPEK ɹɜɥɹɟɬɫɹ ɜɨɡɦɨɠɧɨɫɬɶ ɢɡɛɢɪɚɬɟɥɶɧɨɝɨ ɢ ɦɹɝɤɨɝɨ ɷɤɫɬɪɚɝɢɪɨ91 ɜɚɧɢɹ ɤɨɦɩɨɧɟɧɬɨɜ ɫɭɛɤɥɟɬɨɱɧɵɯ ɫɬɪɭɤɬɭɪ ɫɩɟɰɢɚɥɶɧɵɦɢ ɫɦɟɫɹɦɢ ɪɟɚɝɟɧɬɨɜ. Ȼɥɚɝɨɞɚɪɹ ɷɬɨɦɭ, ɰɟɥɵɣ ɩɪɨɬɟɨɦ ɩɪɟɜɪɚɳɚɟɬɫɹ ɜ ɫɭɛɩɪɨɬɟɨɦɵ ɦɟɧɶɲɟɣ ɫɥɨɠɧɨɫɬɢ ɜ ɨɬɧɨɲɟɧɢɢ ɫɜɨɟɝɨ ɫɨɫɬɚɜɚ. ɉɨɷɬɚɩɧɨɟ ɩɪɢɦɟɧɟɧɢɟ ɬɪɟɯ ɛɭɮɟɪɧɵɯ ɫɦɟɫɟɣ ɩɨɡɜɨɥɹɟɬ ɩɨɫɥɟɞɨɜɚɬɟɥɶɧɨ ɜɵɞɟɥɢɬɶ ɬɪɢ ɮɪɚɤɰɢɢ ɛɟɥɤɨɜ ɫ ɪɚɫɬɜɨɪɢɦɨɫɬɶɸ, ɢɡɦɟɧɹɸɳɟɣɫɹ ɨɬ ɦɚɤɫɢɦɚɥɶɧɨɣ ɤ ɦɢɧɢɦɚɥɶɧɨɣ. ɇɚ ɫɥɟɞɭɸɳɟɣ ɫɬɚɞɢɢ ɪɚɛɨɬɵ ɩɪɢɦɟɧɹɟɬɫɹ ɧɚɛɨɪ ɪɟɚɝɟɧɬɨɜ 2D Clean-Up Kit (Amersham Biosciences), ɡɚɜɟɪɲɚɸɳɢɣ ɢ ɨɩɬɢɦɢɡɢɪɭɸɳɢɣ ɩɨɞɝɨɬɨɜɤɭ ɨɛɪɚɡɰɨɜ ɤ ɞɜɭɦɟɪɧɨɦɭ ɝɟɥɶ-ɷɥɟɤɬɪɨɮɨɪɟɡɭ. ɗɬɢ ɪɟɚɝɟɧɬɵ ɤɨɥɢɱɟɫɬɜɟɧɧɨ ɨɫɚɠɞɚɸɬ ɛɟɥɤɢ, ɨɫɬɚɜɥɹɹ ɩɨɦɟɯɨɨɛɪɚɡɭɸɳɢɟ ɫɨɟɞɢɧɟɧɢɹ ɜ ɪɚɫɬɜɨɪɟɧɧɨɦ ɫɨɫɬɨɹɧɢɢ. ɋɩɨɫɨɛɧɨɫɬɶ ɉɌȽ ɫɬɢɦɭɥɢɪɨɜɚɬɶ ɩɪɨɥɢɮɟɪɚɰɢɸ ɪɚɧɧɢɯ ɤɪɨɜɟɬɜɨɪɧɵɯ ɩɪɟɞɲɟɫɬɜɟɧɧɢɤɨɜ, ɜɟɪɨɹɬɧɨ, ɦɨɠɧɨ ɢɫɩɨɥɶɡɨɜɚɬɶ ɞɥɹ ɷɤɫɩɚɧɫɢɢ ȽɋɄ [2]. Ɍɚɤɢɦ ɨɛɪɚɡɨɦ, ɧɚɦɢ ɧɟ ɬɨɥɶɤɨ ɩɨɥɭɱɟɧɵ ɞɚɧɧɵɟ ɩɨ ɩɪɨɬɟɨɦɧɨɦɭ ɩɪɨɮɢɥɸ ɨɫɬɟɨɛɥɚɫɬɨɜ, ɧɨ ɢ ɫɞɟɥɚɧ ɨɱɟɪɟɞɧɨɣ ɲɚɝ ɤ ɢɡɭɱɟɧɢɸ ɜɨɡɦɨɠɧɨɫɬɢ ɜɨɡɞɟɣɫɬɜɢɹ ɧɚ ɤɪɨɜɟɬɜɨɪɧɵɟ «ɧɢɲɢ» ɢɥɢ ɧɚ ɦɨɥɟɤɭɥɵ ɫɢɝɧɚɥɶɧɵɯ ɩɭɬɟɣ ɜɡɚɢɦɨɞɟɣɫɬɜɢɹ ȽɋɄ ɫ ɦɢɤɪɨɨɤɪɭɠɟɧɢɟɦ ɞɥɹ ɫɬɢɦɭɥɹɰɢɢ ɢɯ ɪɨɫɬɚ. 4.2 ɏɚɪɚɤɬɟɪɢɫɬɢɤɚ ɝɟɦɨɩɨɷɬɢɱɟɫɤɢɯ ɫɬɜɨɥɨɜɵɯ ɤɥɟɬɨɤ 4.2.1 Ȼɟɥɤɨɜɵɣ ɩɪɨɮɢɥɶ ɦɨɧɨɧɭɤɥɟɚɪɧɵɯ ɤɥɟɬɨɤ ɇɟɫɦɨɬɪɹ ɧɚ ɩɪɨɢɫɯɨɠɞɟɧɢɟ ɨɛɪɚɡɰɨɜ ɆɇɄ ɢɡ ɨɞɧɨɣ ɚɥɢɤɜɨɬɵ ɉɄ, ɛɟɥɤɨɜɵɟ ɩɪɨɮɢɥɢ ɨɛɪɚɡɰɨɜ Ⱥ ɢ Ȼ ɨɛɧɚɪɭɠɢɥɢ ɧɟɛɨɥɶɲɢɟ ɨɬɥɢɱɢɹ. Ɉɛɪɚɡɰɵ ɯɪɚɧɢɥɢɫɶ ɜ ɫɯɨɞɧɵɯ ɭɫɥɨɜɢɹɯ, ɚ ɪɚɫɯɨɠɞɟɧɢɹ ɜ ɞɚɧɧɵɯ, ɤɚɤ ɩɪɟɞɫɬɚɜɥɹɟɬɫɹ, ɨɛɭɫɥɨɜɥɟɧɵ ɪɚɡɥɢɱɧɵɦɢ ɜɧɟɲɧɢɦɢ ɮɚɤɬɨɪɚɦɢ ɷɤɫɩɟɪɢɦɟɧɬɚ. ɇɚɩɪɢɦɟɪ, ɢɫɬɨɱɧɢɤɚɦɢ ɬɚɤɢɯ ɪɚɫɯɨɠɞɟ- 92 ɧɢɣ ɦɨɝɭɬ ɛɵɬɶ ɩɨɥɢɚɤɪɢɥɚɦɢɞɧɵɟ ɝɟɥɢ, ɢɫɩɨɥɶɡɭɟɦɵɟ ɞɥɹ ɷɤɫɩɟɪɢɦɟɧɬɨɜ. Ɉɛɚ ɧɚɩɪɚɜɥɟɧɢɹ ɪɚɡɞɟɥɟɧɢɹ ɫ ɩɨɦɨɳɶɸ ɷɥɟɤɬɪɨɮɨɪɟɡɚ ɩɪɟɞɩɨɥɚɝɚɸɬ ɢɫɩɨɥɶɡɨɜɚɧɢɟ ɪɚɡɧɵɯ ɝɟɥɟɣ ɞɥɹ ɤɚɠɞɨɝɨ ɨɛɪɚɡɰɚ, ɩɨɷɬɨɦɭ ɪɚɡɥɢɱɢɹ ɜ ɝɟɥɹɯ ɦɨɝɭɬ ɩɪɢɜɟɫɬɢ ɤ ɪɚɫɯɨɠɞɟɧɢɹɦ ɜ ɪɟɡɭɥɶɬɚɬɚɯ. Ⱦɥɹ ɦɢɧɢɦɢɡɚɰɢɢ ɷɬɨɝɨ ɜɥɢɹɧɢɹ ɦɨɠɧɨ ɢɫɩɨɥɶɡɨɜɚɬɶ ɩɪɟɞɜɚɪɢɬɟɥɶɧɨ ɨɬɨɛɪɚɧɧɵɟ ɝɟɥɢ ɩɨɜɵɲɟɧɧɨɣ ɫɬɚɛɢɥɶɧɨɫɬɢ, ɫ ɜɨɫɩɪɨɢɡɜɨɞɢɦɨɫɬɶɸ, ɡɚɜɢɫɹɳɟɣ ɨɬ ɨɛɨɪɭɞɨɜɚɧɢɹ, ɩɪɢɦɟɧɹɟɦɨɝɨ ɩɪɨɢɡɜɨɞɢɬɟɥɟɦ. ȼ ɩɟɪɜɨɟ ɧɚɩɪɚɜɥɟɧɢɟ ɪɚɡɞɟɥɟɧɢɹ ɜɨɜɥɟɱɟɧɵ IPG-ɫɬɪɢɩɵ, ɤɨɬɨɪɵɟ ɢɦɟɸɬ ɨɫɚɞɨɱɧɵɣ ɝɪɚɞɢɟɧɬ ɪɇ (3-11 ɜ ɧɚɲɟɦ ɫɥɭɱɚɟ). ȼɚɪɢɚɰɢɢ ɜ ɢɦɦɨɛɢɥɢɡɨɜɚɧɧɵɯ ɷɥɟɤɬɪɨɥɢɬɚɯ, ɢɫɩɨɥɶɡɭɟɦɵɯ ɞɥɹ ɫɨɡɞɚɧɢɹ ɝɪɚɞɢɟɧɬɚ, ɩɪɢɜɨɞɹɬ ɤ ɫɦɟɳɟɧɢɸ ɛɟɥɤɨɜɵɯ ɩɹɬɟɧ ɜɞɨɥɶ ɨɫɢ ɏ (ɩɟɪɜɨɟ ɧɚɩɪɚɜɥɟɧɢɟ ɪɚɡɞɟɥɟɧɢɹ) ɜ ɪɟɡɭɥɶɬɢɪɭɸɳɟɦ ɝɟɥɟ. ȼɨ ɜɬɨɪɨɦ ɧɚɩɪɚɜɥɟɧɢɢ ɪɚɡɞɟɥɟɧɢɹ ɩɥɨɬɧɨɫɬɶ ɝɪɚɞɢɟɧɬɧɨ-ɭɩɚɤɨɜɚɧɧɨɝɨ (4–12%) ɉȺȺȽ ɬɚɤɠɟ ɦɨɠɟɬ ɩɪɢɜɟɫɬɢ ɤ ɜɚɪɢɚɛɟɥɶɧɨɫɬɢ. ȼɟɥɢɱɢɧɚ ɩɹɬɧɚ ɦɨɠɟɬ ɧɚɛɥɸɞɚɬɶɫɹ ɢ ɤɚɤ «ɦɨɧɬɚɠɧɵɣ ɨɛɪɚɡ», ɩɪɟɞɫɬɚɜɥɹɸɳɢɣ ɫɨɛɨɣ ɬɪɟɯɦɟɪɧɨɟ ɢɡɨɛɪɚɠɟɧɢɟ ɛɟɥɤɨɜɨɝɨ ɩɹɬɧɚ. Ɍɪɟɯɦɟɪɧɵɣ ɢɧɫɬɪɭɦɟɧɬ ɜɢɡɭɚɥɢɡɚɰɢɢ («ɦɨɧɬɚɠɧɵɣ ɨɛɪɚɡ») ɩɨɡɜɨɥɹɟɬ ɩɪɨɜɨɞɢɬɶ ɛɨɥɟɟ ɬɳɚɬɟɥɶɧɨɟ ɢɫɫɥɟɞɨɜɚɧɢɟ ɛɟɥɤɨɜɵɯ ɩɹɬɟɧ. Ɍɚɤɨɣ ɩɨɞɯɨɞ ɦɨɠɟɬ ɢɫɩɨɥɶɡɨɜɚɬɶɫɹ ɭɬɨɱɧɟɧɢɹ ɤɚɤɢɯ-ɥɢɛɨ ɫɜɟɞɟɧɢɣ ɢ ɨɛɧɚɪɭɠɟɧɢɹ ɢɡɦɟɧɟɧɢɣ ɜ ɛɟɥɤɨɜɵɯ ɭɪɨɜɧɹɯ. Ʉɨɧɤɪɟɬɧɵɟ ɬɨɱɤɢ ɦɨɝɭɬ ɛɵɬɶ ɨɬɨɛɪɚɧɵ ɢ ɢɡɭɱɟɧɵ ɛɨɥɟɟ ɩɨɞɪɨɛɧɨ ɞɥɹ ɧɚɛɥɸɞɟɧɢɹ ɢɡɦɟɧɟɧɢɣ ɢɥɢ ɤɨɧɫɬɚɬɚɰɢɢ ɢɯ ɨɬɫɭɬɫɬɜɢɹ. ɗɬɨ ɜɚɠɧɨ ɞɥɹ ɩɨɞɬɜɟɪɠɞɟɧɢɹ ɭɜɟɪɟɧɧɨɫɬɢ ɜ ɪɟɡɭɥɶɬɚɬɚɯ ɚɜɬɨɦɚɬɢɡɢɪɨɜɚɧɧɨɝɨ ɢ ɤɨɦɩɶɸɬɟɪɧɨɝɨ ɚɧɚɥɢɡɚ. Ɉɞɧɢɦ ɢɡ ɨɫɧɨɜɧɵɯ ɬɪɟɛɨɜɚɧɢɣ ɤ ɩɪɨɬɟɨɦɢɤɟ ɤɚɤ ɤ ɢɧɫɬɪɭɦɟɧɬɭ ɞɥɹ ɦɨɧɢɬɨɪɢɧɝɚ ɢɡɦɟɧɟɧɢɣ ɛɟɥɤɚ ɹɜɥɹɟɬɫɹ ɫɩɨɫɨɛɧɨɫɬɶ ɨɛɧɚɪɭɠɢɜɚɬɶ ɷɬɢ ɢɡɦɟɧɟɧɢɹ ɢ ɢɯ ɜɟɥɢɱɢɧɭ. Ɍɚɤɢɦ ɨɛɪɚɡɨɦ, ɬɪɟɛɭɟɬɫɹ ɢɫ93 ɤɥɸɱɟɧɢɟ ɢɡ ɪɚɫɫɦɨɬɪɟɧɢɹ ɨɲɢɛɨɱɧɵɯ ɪɟɡɭɥɶɬɚɬɨɜ (ɜ ɮɨɪɦɟ ɡɚɝɪɹɡɧɟɧɢɣ, ɮɨɧɨɜɵɯ ɲɭɦɨɜ, ɩɥɨɯɢɯ ɷɤɫɩɟɪɢɦɟɧɬɚɥɶɧɵɯ ɩɪɨɰɟɞɭɪ ɢɥɢ ɩɪɨɫɬɨ ɧɟɞɨɫɬɚɬɨɱɧɨ ɡɧɚɱɢɦɵɯ ɢɡɦɟɧɟɧɢɣ), ɜɥɢɹɸɳɢɯ ɧɚ ɧɚɲɭ ɫɩɨɫɨɛɧɨɫɬɶ ɜɵɹɜɥɹɬɶ ɧɚɢɛɨɥɟɟ ɡɧɚɱɢɦɵɟ. Ⱥ ɢɦɢ ɹɜɥɹɸɬɫɹ ɢɡɦɟɧɟɧɢɹ ɛɟɥɤɨɜ, ɦɨɞɢɮɢɰɢɪɭɸɳɢɟ ɛɢɨɥɨɝɢɱɟɫɤɭɸ ɚɤɬɢɜɧɨɫɬɶ. ȼ ɷɬɨɣ ɫɜɹɡɢ ɧɚɦɢ ɩɪɟɞɥɨɠɟɧɵ ɩɨɪɨɝɨɜɵɟ ɡɧɚɱɟɧɢɹ ɜ ɜɢɞɟ ɤɨɷɮɮɢɰɢɟɧɬɚ, ɨɩɪɟɞɟɥɹɸɳɟɝɨ ɤɪɚɬɧɨɫɬɶ ɭɜɟɥɢɱɟɧɢɹ (ɢɥɢ ɭɦɟɧɶɲɟɧɢɹ) ɪɚɡɦɟɪɚ ɛɟɥɤɨɜɨɝɨ ɩɹɬɧɚ. ɑɭɜɫɬɜɢɬɟɥɶɧɨɫɬɶ ɩɨ ɨɬɧɨɲɟɧɢɸ ɤ ɨɛɧɚɪɭɠɟɧɢɸ ɛɟɥɤɨɜɨɝɨ ɩɹɬɧɚ ɡɚɜɢɫɢɬ ɨɬ ɬɪɟɯ ɩɚɪɚɦɟɬɪɨɜ: 1) ɷɮɮɟɤɬɢɜɧɨɫɬɢ ɤɪɚɫɢɬɟɥɹ ɞɥɹ ɨɤɪɚɫɤɢ ɛɟɥɤɚ; 2) ɬɟɯɧɨɥɨɝɢɢ ɫɤɚɧɢɪɨɜɚɧɢɹ ɞɥɹ ɩɨɥɭɱɟɧɢɹ ɢɡɨɛɪɚɠɟɧɢɹ ɝɟɥɹ; 3) ɫɩɨɫɨɛɧɨɫɬɢ ɩɪɨɝɪɚɦɦɧɨɝɨ ɨɛɟɫɩɟɱɟɧɢɹ ɨɬɥɢɱɚɬɶ ɩɹɬɧɚ ɨɬ ɮɨɧɚ. ɇɨ ɹɫɧɨ, ɱɬɨ ɜɫɟ ɷɬɢ ɮɚɤɬɨɪɵ ɜɧɭɬɪɟɧɧɟ ɨɩɨɫɪɟɞɨɜɚɧɵ ɤɨɥɢɱɟɫɬɜɨɦ ɩɪɢɫɭɬɫɬɜɭɸɳɟɝɨ ɛɟɥɤɚ. ɂɫɯɨɞɹ ɢɡ ɩɪɟɞɩɨɥɨɠɟɧɢɹ, ɱɬɨ ɩɟɪɜɵɟ ɞɜɚ ɮɚɤɬɨɪɚ ɹɜɥɹɸɬɫɹ ɩɨɫɬɨɹɧɧɵɦɢ ɜ ɪɚɦɤɚɯ ɨɞɧɨɝɨ ɷɤɫɩɟɪɢɦɟɧɬɚ, ɬɚɤ ɤɚɤ ɨɧɢ ɧɟ ɫɜɹɡɚɧɵ ɫ ɨɛɪɚɡɰɚɦɢ, ɩɪɨɝɪɚɦɦɧɨɟ ɨɛɟɫɩɟɱɟɧɢɟ – ɟɞɢɧɫɬɜɟɧɧɵɣ ɢɫɬɨɱɧɢɤ ɨɝɪɚɧɢɱɟɧɢɣ ɩɪɢ ɨɛɧɚɪɭɠɟɧɢɢ ɛɟɥɤɨɜɵɯ ɩɹɬɟɧ. Ɉɞɧɚɤɨ ɨɧɨ ɱɭɜɫɬɜɢɬɟɥɶɧɨ ɤ ɜɚɪɢɚɛɟɥɶɧɨɫɬɢ ɦɟɠɞɭ ɨɛɪɚɡɰɚɦɢ. ȼ ɱɚɫɬɧɨɫɬɢ, ɩɪɨɝɪɚɦɦɚ ɨɫɭɳɟɫɬɜɥɹɟɬ ɜɵɱɢɬɚɧɢɟ ɮɨɧɚ ɞɥɹ ɜɵɞɟɥɟɧɢɹ ɛɟɥɤɨɜɵɯ ɩɹɬɟɧ ɢ ɨɰɟɧɤɢ ɢɯ ɜɟɥɢɱɢɧɵ. ɗɬɚ ɫɩɨɫɨɛɧɨɫɬɶ ɢɞɟɧɬɢɮɢɰɢɪɨɜɚɬɶ ɩɹɬɧɚ ɨɩɪɟɞɟɥɟɧɚ ɤɚɤ ɧɢɠɧɢɣ ɩɪɟɞɟɥ ɱɭɜɫɬɜɢɬɟɥɶɧɨɫɬɢ (ɪɢɫ. 4.1ɛ). ȼɟɪɯɧɢɣ ɩɪɟɞɟɥ ɱɭɜɫɬɜɢɬɟɥɶɧɨɫɬɢ (ɪɢɫ. 4.1ɚ) ɨɩɪɟɞɟɥɹɟɬɫɹ ɤɚɤ ɫɩɨɫɨɛɧɨɫɬɶ ɩɪɨɝɪɚɦɦɵ ɭɫɬɚɧɨɜɢɬɶ ɦɚɤɫɢɦɚɥɶɧɭɸ ɤɨɧɰɟɧɬɪɚɰɢɸ ɤɨɧɤɪɟɬɧɨɝɨ ɛɟɥɤɨɜɨɝɨ ɩɹɬɧɚ. ɉɨ ɫɭɬɢ, ɷɬɨɬ ɩɪɟɞɟɥ ɹɜɥɹɟɬɫɹ ɦɚɤɫɢɦɚɥɶɧɨɣ ɢɧɬɟɧɫɢɜɧɨɫɬɶɸ ɛɟɥɤɨɜɨɝɨ ɩɹɬɧɚ, ɜɵɲɟ ɤɨɬɨɪɨɣ ɢɧɬɟɧɫɢɜɧɨɫɬɢ ɧɟ ɪɟɝɢɫɬɪɢɪɭɟɬɫɹ. ȼ ɛɨɥɟɟ ɩɪɨɫɬɨɣ ɬɟɪɦɢɧɨɥɨɝɢɢ, ɷɬɨ ɫɚɦɚɹ ɬɟɦɧɚɹ ɬɨɱɤɚ ɩɹɬɧɚ ɧɚ ɝɟɥɟ, ɤɨɬɨɪɚɹ ɧɟ ɦɨɠɟɬ ɛɵɬɶ ɢɡɦɟɪɟɧɚ ɤɚɤ 94 ɩɪɨɰɟɧɬ ɫɟɪɵɯ ɩɹɬɟɧ ɦɟɠɞɭ ɫɚɦɨɣ ɜɵɫɨɤɨɣ ɢ ɫɚɦɨɣ ɧɢɡɤɨɣ ɢɧɬɟɧɫɢɜɧɨɫɬɶɸ. ɋɚɦɚɹ ɬɟɦɧɚɹ ɬɨɱɤɚ ɧɟ ɦɨɠɟɬ ɛɵɬɶ ɨɩɢɫɚɧɚ ɜɟɥɢɱɢɧɨɣ, ɫɜɹɡɚɧɧɨɣ ɫ ɞɪɭɝɢɦɢ ɢɧɬɟɧɫɢɜɧɨɫɬɹɦɢ ɩɢɤɨɜ. ɗɬɨ ɢɦɟɧɧɨ ɬɚ ɬɨɱɤɚ, ɤɨɝɞɚ ɞɨɫɬɢɝɚɟɬɫɹ ɜɟɪɯɧɢɣ ɩɪɟɞɟɥ ɱɭɜɫɬɜɢɬɟɥɶɧɨɫɬɢ. ȼɟɪɯɧɢɣ ɩɪɟɞɟɥ ɨɩɪɟɞɟɥɹɟɬɫɹ ɤɨɦɩɶɸɬɟɪɧɵɦ ɪɟɲɟɧɢɟɦ ɢ ɬɟɯɧɨɥɨɝɢɣ ɨɤɪɚɲɢɜɚɧɢɹ. Ⱦɢɧɚɦɢɱɟɫɤɢɣ ɩɨɤɚɡɚɬɟɥɶ-ɢɧɬɟɪɜɚɥ («range of») 2,5×103 ɨɡɧɚɱɚɟɬ, ɱɬɨ ɭɜɟɥɢɱɟɧɢɟ ɢɧɬɟɧɫɢɜɧɨɫɬɢ ɩɢɤɚ ɫɨɫɬɚɜɥɹɟɬ 2,5×103 ɪɚɡ, ɱɬɨ ɢ ɧɚɛɥɸɞɚɟɬɫɹ ɞɥɹ 1-ɣ ɮɪɚɤɰɢɢ ɨɛɪɚɡɰɚ ɆɇɄ (ɪɢɫ. 4.1). ɚ ɛ Ɋɢɫ. 4.1. ȼɟɪɯɧɢɣ (ɚ) ɢ ɧɢɠɧɢɣ (ɛ) ɩɪɟɞɟɥɵ ɱɭɜɫɬɜɢɬɟɥɶɧɨɫɬɢ ɩɪɢ ɨɛɧɚɪɭɠɟɧɢɢ ɛɟɥɤɨɜɵɯ ɩɹɬɟɧ ɉɪɟɞɟɥɵ ɱɭɜɫɬɜɢɬɟɥɶɧɨɫɬɢ ɫɢɥɶɧɨ ɡɚɜɢɫɹɬ ɨɬ ɤɨɥɢɱɟɫɬɜɚ ɧɚɧɟɫɟɧɧɨɝɨ ɛɟɥɤɚ. ɑɟɦ ɛɨɥɶɲɟ ɛɟɥɤɚ ɧɚɧɟɫɟɧɨ ɧɚ ɝɟɥɶ, ɬɟɦ ɛɨɥɟɟ ɜɟɪɨɹɬɧɨ, ɱɬɨ ɩɨɥɭɱɟɧɧɵɟ ɛɟɥɤɨɜɵɟ ɩɹɬɧɚ ɞɨɫɬɢɝɧɭɬ ɫɜɨɟɝɨ ɜɟɪɯɧɟɝɨ ɩɪɟɞɟɥɚ ɱɭɜɫɬɜɢɬɟɥɶɧɨɫɬɢ. ɇɚɧɟɫɟɧɢɟ ɧɚ ɝɟɥɶ ɧɟɞɨɫɬɚɬɨɱɧɨɝɨ ɤɨɥɢɱɟɫɬɜɚ ɛɟɥɤɚ ɩɪɢɜɨɞɢɬ ɤ ɩɨɥɭɱɟɧɢɸ ɛɟɥɤɨɜɵɯ ɩɹɬɟɧ, ɞɨɫɬɢɝɚɸɳɢɯ ɫɜɨɟɝɨ ɧɢɠɧɟɝɨ ɩɪɟɞɟɥɚ ɱɭɜɫɬɜɢɬɟɥɶɧɨɫɬɢ. Ɍɚɤɢɦ ɨɛɪɚɡɨɦ, ɨɱɟɧɶ ɜɚɠɧɨ ɧɚɧɨɫɢɬɶ ɧɚ ɝɟɥɶ ɬɚɤɢɟ ɤɨɥɢɱɟɫɬɜɚ ɛɟɥɤɚ, ɱɬɨɛɵ ɩɹɬɚ ɨɤɚɡɵɜɚɥɢɫɶ ɜɧɭɬɪɢ ɞɢɧɚɦɢɱɟɫɤɨɝɨ ɢɧɬɟɪɜɚɥɚ. ȼ ɫɜɨɸ ɨɱɟɪɟɞɶ, ɤɨɥɢɱɟɫɬɜɨ ɧɚɧɟɫɟɧɧɨɝɨ ɛɟɥɤɚ ɹɜɥɹɟɬɫɹ ɮɭɧɤɰɢɟɣ ɱɢɫɥɚ ɤɥɟɬɨɤ. 95 4.2.2 Ȼɟɥɤɨɜɵɣ ɩɪɨɮɢɥɶ CD34+ ȽɋɄ ȽɋɄ ɱɟɥɨɜɟɤɚ ɨɛɧɚɪɭɠɟɧɵ ɜ ɩɨɩɭɥɹɰɢɢ ɤɥɟɬɨɤ, ɷɤɫɩɪɟɫɫɢɪɭɸɳɢɯ ɜɵɫɨɤɢɣ ɭɪɨɜɟɧɶ ɚɧɬɢɝɟɧɚ CD34 (CD34+), ɯɨɬɹ ɨɞɧɢɦ ɢɡ ɞɪɭɝɢɯ ɤɪɢɬɟɪɢɟɜ ɹɜɥɹɟɬɫɹ ɨɬɫɭɬɫɬɜɢɟ ɚɧɬɢɝɟɧɚ CD38 (CD38–) ɢ, ɬɚɤɢɦ ɨɛɪɚɡɨɦ, ɢɫɬɢɧɧɵɟ ȽɋɄ ɨɩɪɟɞɟɥɹɸɬɫɹ ɤɚɤ CD34+CD38– (55). Ɉɛɵɱɧɨɣ ɩɪɚɤɬɢɤɨɣ ɹɜɥɹɟɬɫɹ ɪɚɫɫɦɚɬɪɢɜɚɬɶ ȽɋɄ ɤɚɤ CD34+ ɜ ɫɜɹɡɢ ɫ ɬɟɦ, ɱɬɨ ɨɛɧɚɪɭɠɟɧɢɟ ɚɧɬɢɝɟɧɚ CD34 ɩɪɟɞɲɟɫɬɜɭɟɬ ɬɪɚɧɫɩɥɚɧɬɚɰɢɢ ɜ ɤɥɢɧɢɤɟ ɢ ɫɨɡɞɚɧɢɸ ɛɚɧɤɚ ɩɭɩɨɜɢɧɧɨɣ ɤɪɨɜɢ. Ⱦɥɹ ɰɟɥɟɣ ɩɪɨɬɟɨɦɧɨɝɨ ɚɧɚɥɢɡɚ ɩɪɢɧɹɬɨ ɧɚɡɜɚɧɢɟ «ɩɨɩɭɥɹɰɢɹ CD34+ ȽɋɄ», ɜɤɥɸɱɚɸɳɚɹ ɤɥɟɬɤɢ CD38+ ɢ CD38–. Ɉɞɧɨɣ ɢɡ ɝɥɚɜɧɵɯ ɩɪɢɱɢɧ ɞɥɹ ɷɬɨɝɨ ɹɜɥɹɟɬɫɹ ɬɨɬ ɮɚɤɬ, ɱɬɨ ɭɞɚɥɟɧɢɟ CD38+ ɤɥɟɬɨɤ ɩɪɢɜɨɞɢɬ ɤ ɩɚɞɟɧɢɸ ɨɛɳɟɝɨ ɱɢɫɥɚ ɤɥɟɬɨɤ ɧɢɠɟ ɦɢɧɢɦɭɦɚ (2×106), ɧɟɨɛɯɨɞɢɦɨɝɨ ɞɥɹ ɩɪɨɬɟɨɦɧɨɝɨ ɚɧɚɥɢɡɚ. ɋ ɭɱɟɬɨɦ ɬɨɝɨ ɮɚɤɬɚ, ɱɬɨ ɤɥɢɧɢɰɢɫɬɵ ɬɪɚɧɫɩɥɚɧɬɢɪɭɸɬ ɜɟɫɶ ɨɛɪɚɡɟɰ ɩɭɩɨɜɢɧɧɨɣ ɤɪɨɜɢ, ɤɨɬɨɪɵɣ ɜɤɥɸɱɚɟɬ ɜ ɫɜɨɣ ɫɨɫɬɚɜ ɦɧɨɝɨɹɞɟɪɧɵɟ ɤɥɟɬɤɢ, ɆɇɄ (ɧɟɤɨɬɨɪɵɟ ɢɡ ɤɨɬɨɪɵɯ ɹɜɥɹɸɬɫɹ CD34– ɢ CD38+), ɩɪɨɬɟɨɦɧɵɣ ɚɧɚɥɢɡ, ɫɨɡɞɚɧɧɵɣ ɞɥɹ ɢɡɭɱɟɧɢɹ ɤɥɟɬɨɤ CD34+, ɞɚɟɬ ɮɚɤɬɢɱɟɫɤɢɟ ɯɚɪɚɤɬɟɪɢɫɬɢɤɢ ɷɬɢɯ ɫɬɜɨɥɨɜɵɯ ɤɥɟɬɨɤ ɢ ɩɨɡɜɨɥɹɟɬ ɥɭɱɲɟ ɩɨɧɹɬɶ ɫɜɨɣɫɬɜɚ ȽɋɄ. ɋ ɞɪɭɝɨɣ ɫɬɨɪɨɧɵ, ɦɨɠɧɨ ɧɚɣɬɢ ɢ ɛɢɨɥɨɝɢɱɟɫɤɨɟ ɨɛɴɹɫɧɟɧɢɟ ɢ ɩɪɟɞɩɨɥɨɠɢɬɶ, ɱɬɨ ɬɚɤɨɟ ɬɪɟɛɨɜɚɧɢɟ ɤ ɤɨɥɢɱɟɫɬɜɭ ɤɥɟɬɨɤ CD34+ ɩɨ ɫɪɚɜɧɟɧɢɸ ɫ ɨɫɬɟɨɛɥɚɫɬɚɦɢ ɢ ɆɇɄ ɨɛɴɹɫɧɹɟɬɫɹ ɫɚɪɤɨɦɧɨɣ ɩɪɢɪɨɞɨɣ ɤɥɟɬɨɤ MG63 ɢ ɛɨɥɶɲɟɣ ɡɪɟɥɨɫɬɶɸ ɆɇɄ ɩɨ ɫɪɚɜɧɟɧɢɸ ɫ CD34+ ɤɥɟɬɤɚɦɢ, ɤɨɬɨɪɵɟ ɢɦɟɸɬ ɢ ɛɨɥɟɟ ɧɢɡɤɢɣ ɭɪɨɜɟɧɶ ɛɟɥɤɚ. ɉɪɢɱɢɧɚ ɞɥɹ ɢɫɩɨɥɶɡɨɜɚɧɢɹ ɩɨɤɚɡɚɬɟɥɹ «ɱɢɫɥɨ ɤɥɟɬɨɤ», ɚ ɧɟ «ɚɛɫɨɥɸɬɧɨɟ ɤɨɥɢɱɟɫɬɜɨ ɛɟɥɤɚ» – ɛɨɥɟɟ ɚɞɟɤɜɚɬɧɨɟ ɩɪɟɞɫɬɚɜɥɟɧɢɟ ɢɫɫɥɟɞɭɟɦɨɣ ɤɥɟɬɨɱɧɨɣ ɩɨɩɭɥɹɰɢɢ, ɩɪɢɱɟɦ ɩɪɢɧɢɦɚɟɬɫɹ ɜɨ ɜɧɢɦɚɧɢɟ ɢ ɤɨ- 96 ɥɢɱɟɫɬɜɨ ɛɟɥɤɚ. Ʉ ɬɨɦɭ ɠɟ ɩɨɞɯɨɞ «ɱɢɫɥɨ ɤɥɟɬɨɤ» ɩɨɡɜɨɥɹɟɬ ɭɱɢɬɵɜɚɬɶ ɧɟ ɬɨɥɶɤɨ ɬɚɤɢɟ ɞɨɦɢɧɢɪɭɸɳɢɟ ɛɟɥɤɢ, ɤɚɤ ɚɥɶɛɭɦɢɧ, ɧɨ ɢ ɦɟɧɟɟ ɡɚɦɟɬɧɵɟ, ɤɨɬɨɪɵɟ ɦɨɝɥɢ ɛɵ ɛɵɬɶ ɭɬɟɪɹɧɵ ɩɪɢ ɫɧɢɠɟɧɢɢ ɤɨɧɰɟɧɬɪɚɰɢɢ ɛɟɥɤɨɜ ɞɨ ɬɪɟɛɭɟɦɨɣ ɜɟɥɢɱɢɧɵ. Ɉɩɬɢɦɚɥɶɧɨɟ ɜɧɟɫɟɧɢɟ ɨɛɪɚɡɰɚ ɜ ɝɟɥɶ, ɬɚɤɢɦ ɨɛɪɚɡɨɦ, ɛɭɞɟɬ ɡɚɜɢɫɟɬɶ ɨɬ ɭɪɨɜɧɹ ɷɤɫɬɪɚɝɢɪɨɜɚɧɧɨɝɨ ɛɟɥɤɚ ɤɚɤ ɮɭɧɤɰɢɢ ɢɫɩɨɥɶɡɨɜɚɧɧɨɝɨ ɱɢɫɥɚ ɤɥɟɬɨɤ. Ȼɨɥɟɟ ɬɨɝɨ, ɩɨɞɫɱɟɬ ɤɥɟɬɨɤ ɛɨɥɟɟ ɫɨɜɦɟɫɬɢɦ ɫ ɚɥɝɨɪɢɬɦɨɦ ɚɧɚɥɢɡɚ, ɥɟɝɱɟ ɤɨɧɬɪɨɥɢɪɭɟɬɫɹ ɢ ɩɪɢɫɩɨɫɨɛɥɟɧ ɞɥɹ ɢɡɭɱɟɧɢɹ ɤɭɥɶɬɭɪɵ ɤɥɟɬɨɤ, ɝɞɟ ɢɯ ɩɨɞɫɱɟɬ – ɪɭɬɢɧɧɚɹ ɩɪɨɰɟɞɭɪɚ. ɉɨɤɚɡɚɬɟɥɶ «ɱɢɫɥɨ ɤɥɟɬɨɤ» ɨɛɟɫɩɟɱɢɜɚɟɬ ɛɨɥɶɲɭɸ ɭɧɢɜɟɪɫɚɥɶɧɨɫɬɶ ɢ ɫɬɚɧɞɚɪɬɢɡɚɰɢɸ ɤɥɟɬɨɱɧɨɝɨ ɩɪɨɬɟɨɦɧɨɝɨ ɚɧɚɥɢɡɚ. ɑɢɫɥɨ ɤɥɟɬɨɤ, ɬɪɟɛɭɟɦɵɯ ɞɥɹ ɚɧɚɥɢɡɚ CD34+ ȽɋɄ, ɫɨɫɬɚɜɥɹɟɬ 2×106, ɱɬɨ ɫɨɨɬɜɟɬɫɬɜɭɟɬ ɞɜɭɦ ɨɛɪɚɡɰɚɦ ɩɭɩɨɜɢɧɧɨɣ ɤɪɨɜɢ. Ɉɛɪɚɡɰɵ ɩɪɨɯɨɞɹɬ ɩɪɨɰɟɞɭɪɭ ɨɛɴɟɞɢɧɟɧɢɹ ɩɨɫɥɟ ɫɬɚɞɢɢ ɦɚɝɧɢɬɧɨɣ ɫɟɩɚɪɚɰɢɢ ɢ ɩɪɢɝɨɞɧɵ ɞɥɹ ɩɨɥɭɱɟɧɢɹ ɯɚɪɚɤɬɟɪɢɫɬɢɤ ɩɨɩɭɥɹɰɢɢ CD34+ ȽɋɄ. Ʉɚɠɞɵɣ ɨɛɪɚɡɟɰ ɩɭɩɨɜɢɧɧɨɣ ɤɪɨɜɢ ɛɟɪɟɬɫɹ ɨɬ ɨɞɧɨɝɨ ɧɨɜɨɪɨɠɞɟɧɧɨɝɨ ɞɨɧɨɪɚ, ɩɨɷɬɨɦɭ ɨɛɴɟɞɢɧɟɧɢɟ ɨɛɪɚɡɰɨɜ ɨɡɧɚɱɚɟɬ, ɱɬɨ ɚɧɚɥɢɡ ɨɬɪɚɠɚɟɬ ɪɟɡɭɥɶɬɚɬɵ ɞɜɭɯ ɢɧɞɢɜɢɞɭɭɦɨɜ. Ɍɚɤɨɣ ɷɮɮɟɤɬ ɨɛɴɟɞɢɧɟɧɢɹ ɢɫɤɥɸɱɚɟɬ ɜɨɡɦɨɠɧɨɫɬɶ ɪɟɝɢɫɬɪɚɰɢɢ ɪɚɡɥɢɱɢɣ ɦɟɠɞɭ ɢɧɞɢɜɢɞɭɭɦɚɦɢ, ɧɨ ɩɨɡɜɨɥɹɟɬ ɩɪɨɜɨɞɢɬɶ ɞɟɬɚɥɢɡɢɪɨɜɚɧɧɨɟ ɨɩɢɫɚɧɢɟ ɩɨɩɭɥɹɰɢɢ CD34+ ȽɋɄ ɱɟɥɨɜɟɤɚ. ȿɫɥɢ ɧɟɨɛɯɨɞɢɦɨ ɩɪɨɜɟɫɬɢ ɪɚɡɦɧɨɠɟɧɢɟ CD34+ ȽɋɄ in vitro, ɫɥɟɞɭɟɬ ɢɫɩɨɥɶɡɨɜɚɬɶ ɩɪɨɬɟɨɦɧɵɣ ɩɪɨɮɢɥɶ ɨɛɟɡɥɢɱɟɧɧɨɝɨ ɨɛɪɚɡɰɚ ɤɚɤ ɷɬɚɥɨɧ ɫɪɚɜɧɟɧɢɹ. Ɍɚɤɨɣ ɩɨɞɯɨɞ ɧɚɩɨɦɢɧɚɟɬ ɦɟɬɨɞɨɥɨɝɢɸ ɢɡɭɱɟɧɢɹ ɝɟɧɨɦɚ, ɩɪɢ ɤɨɬɨɪɨɣ ɨɩɪɟɞɟɥɹɟɬɫɹ ɩɨɫɥɟɞɨɜɚɬɟɥɶɧɨɫɬɶ ȾɇɄ ɜ ɨɛɟɡɥɢɱɟɧɧɵɯ ɨɛɪɚɡɰɚɯ. Ɍɚɤɢɦ ɨɛɪɚɡɨɦ, ɩɨɥɭɱɚɟɦɵɟ ɪɟɡɭɥɶɬɚɬɵ ɫɨɨɬɜɟɬɫɬɜɭɸɬ ɨɩɢɫɚɧɢɸ ɩɨɩɭɥɹɰɢɢ CD34 +ȽɋɄ ɥɸɞɟɣ ɜ ɰɟɥɨɦ. Ȼɨɥɟɟ ɬɨɝɨ, ɢɫɩɨɥɶɡɨɜɚɧɢɟ ɮɪɚɤɰɢɨɧɢɪɨɜɚɧɢɹ ɩɨɡɜɨɥɹɟɬ ɥɭɱɲɟ ɨɯɚɪɚɤɬɟɪɢɡɨɜɚɬɶ ɪɚɡɧɵɟ ɛɟɥɤɢ ɢ ɞɚɬɶ ɛɨɥɟɟ ɩɨɥɧɭɸ ɤɚɪɬɢɧɭ ɩɪɨ97 ɬɟɨɦɧɨɝɨ ɩɪɨɮɢɥɹ ɩɨɩɭɥɹɰɢɢ CD34+ ȽɋɄ, ɬɨ ɟɫɬɶ ɢɞɟɧɬɢɮɢɰɢɪɨɜɚɬɶ ɛɟɥɤɢ, ɢɡ ɤɨɬɨɪɵɯ ɫɨɫɬɨɢɬ CD34+ ɫɬɜɨɥɨɜɚɹ ɤɥɟɬɤɚ ɢ ɩɨɧɹɬɶ ɢɯ ɮɭɧɤɰɢɨɧɚɥɶɧɵɟ ɨɫɨɛɟɧɧɨɫɬɢ, ɚ ɬɚɤɠɟ ɩɨɩɵɬɚɬɶɫɹ ɜɵɹɫɧɢɬɶ ɡɧɚɱɟɧɢɟ ɧɟɤɨɬɨɪɵɯ ɮɚɤɬɨɪɨɜ, ɜɥɢɹɸɳɢɯ ɧɚ ɜɨɡɧɢɤɧɨɜɟɧɢɟ ɢ ɪɚɡɜɢɬɢɟ ɷɬɢɯ ɭɧɢɤɚɥɶɧɵɯ ɤɥɟɬɨɤ. Ƚɥɚɜɧɚɹ ɬɪɭɞɧɨɫɬɶ, ɩɪɟɩɹɬɫɬɜɭɸɳɚɹ ɢɫɫɥɟɞɨɜɚɧɢɸ ȽɋɄ – ɧɢɡɤɚɹ ɞɨɫɬɭɩɧɨɫɬɶ ɬɚɤɢɯ ɤɥɟɬɨɤ ɢ, ɨɫɨɛɟɧɧɨ, ɦɚɥɵɟ ɤɨɥɢɱɟɫɬɜɚ CD34+ ȽɋɄ. Ɍɨɱɧɟɟ, ɩɪɨɛɥɟɦɚ ɧɟ ɜ ɤɨɥɢɱɟɫɬɜɟ ɞɨɫɬɭɩɧɵɯ ɤɥɟɬɨɤ, ɚ ɜ ɫɥɨɠɧɨɫɬɢ ɫɪɚɜɧɟɧɢɹ ɛɟɥɤɨɜɵɯ ɩɪɨɮɢɥɟɣ, ɩɨɥɭɱɟɧɧɵɯ ɫ ɩɨɦɨɳɶɸ 2D/MALDI-ɩɪɨɬɟɨɦɢɤɢ, ɞɥɹ ɤɥɟɬɨɱɧɵɯ ɩɨɩɭɥɹɰɢɣ ɩɪɢ ɨɝɪɚɧɢɱɟɧɧɨɦ ɱɢɫɥɟ ɤɥɟɬɨɤ. ɉɨɩɵɬɤɢ ɨɫɭɳɟɫɬɜɢɬɶ ɩɪɢɜɨɞɹɬ ɤ ɫɨɦɧɢɬɟɥɶɧɨɣ ɞɨɫɬɨɜɟɪɧɨɫɬɢ ɩɨɥɭɱɟɧɧɵɯ ɪɟɡɭɥɶɬɚɬɨɜ ɢ ɧɟɪɚɰɢɨɧɚɥɶɧɨɦɭ ɢɫɩɨɥɶɡɨɜɚɧɢɸ ɞɨɪɨɝɨɫɬɨɹɳɢɯ ɨɛɪɚɡɰɨɜ ɫɬɜɨɥɨɜɵɯ ɤɥɟɬɨɤ. Ɉɞɢɧ ɢɡ ɦɟɬɨɞɢɱɟɫɤɢɯ ɩɨɞɯɨɞɨɜ ɞɥɹ ɪɟɲɟɧɢɹ ɩɪɨɛɥɟɦɵ ɞɨɫɬɭɩɧɨɫɬɢ ȽɋɄ – ɢɫɩɨɥɶɡɨɜɚɧɢɟ ɞɥɹ ɢɯ ɪɚɡɦɧɨɠɟɧɢɹ Jag1, ɢɦɦɨɛɢɥɢɡɨɜɚɧɧɨɝɨ ɧɚ ɦɢɤɪɨɫɮɟɪɚɯ. Kertesz ɫ ɫɨɬɪɭɞɧɢɤɚɦɢ [48] ɩɨɤɚɡɚɥ, ɱɬɨ ɷɬɢ ɦɢɤɪɨɫɮɟɪɵ ɫɩɨɫɨɛɫɬɜɭɸɬ 2-ɤɪɚɬɧɨɦɭ ɭɜɟɥɢɱɟɧɢɸ ɱɢɫɥɚ ɦɵɲɢɧɵɯ ȽɋɄ ɜ ɤɭɥɶɬɭɪɟ ɜ ɬɟɱɟɧɢɟ 14 ɞɧɟɣ. ɇɟɹɫɧɨ, ɨɞɧɚɤɨ, ɛɭɞɟɬ ɥɢ ɷɬɨɬ ɷɮɮɟɤɬ ɜɨɫɩɪɨɢɡɜɟɞɟɧ ɧɚ ɤɥɟɬɤɚɯ ɱɟɥɨɜɟɤɚ ɢ ɤɚɤɨɜɵ ɛɭɞɭ ɫɜɨɣɫɬɜɚ ɩɨɥɭɱɟɧɧɨɣ ɩɨɩɭɥɹɰɢɢ, ɫɨɯɪɚɧɹɬ ɥɢ ɬɚɤɢɟ ɤɥɟɬɤɢ ɫɜɨɢ ɫɜɨɣɫɬɜɚ. ɂɦɟɧɧɨ ɩɪɨɬɟɨɦɢɤɚ ɛɭɞɟɬ ɫɩɨɫɨɛɫɬɜɨɜɚɬɶ ɩɨɥɭɱɟɧɢɸ ɨɬɜɟɬɚ ɧɚ ɷɬɢ ɜɨɩɪɨɫɵ. ɉɨ ɧɚɲɟɦɭ ɦɧɟɧɢɸ, ɩɪɨɬɟɨɦɢɤɚ ɨɫɬɚɟɬɫɹ ɨɞɧɢɦ ɢɡ ɧɚɢɛɨɥɟɟ ɦɨɳɧɵɯ ɢɧɫɬɪɭɦɟɧɬɨɜ ɢɡɭɱɟɧɢɹ ɛɟɥɤɨɜɨɣ ɷɤɫɩɪɟɫɫɢɢ. Ɉɱɟɧɶ ɜɚɠɧɨ ɞɥɹ ɞɚɥɶɧɟɣɲɟɣ ɪɚɛɨɬɵ ɩɪɚɜɢɥɶɧɨ ɜɵɛɪɚɬɶ ɩɨɩɭɥɹɰɢɸ ɤɥɟɬɨɤ, ɬɚɤ ɤɚɤ ɩɪɨɬɟɨɦɢɤɚ ɢɫɫɥɟɞɭɟɬ ɢɦɟɧɧɨ ɩɨɩɭɥɹɰɢɢ, ɚ ɧɟ ɟɞɢɧɢɱɧɵɟ ɤɥɟɬɤɢ. ɉɨɷɬɨɦɭ ɝɨɦɨɝɟɧɧɨɫɬɶ ɩɨɩɭɥɹɰɢɢ ɤɪɢɬɢɱɧɚ ɞɥɹ ɩɨɥɭɱɟɧɢɹ ɪɟɡɭɥɶɬɚɬɨɜ, ɨɬɪɚɠɚɸɳɢɯ ɟɟ ɛɟɥɤɨɜɭɸ ɫɭɳɧɨɫɬɶ. 98 Ɉɞɧɨ ɢɡ ɧɚɩɪɚɜɥɟɧɢɣ ɩɟɪɫɩɟɤɬɢɜɧɵɯ ɞɚɥɶɧɟɣɲɢɯ ɢɫɫɥɟɞɨɜɚɧɢɣ – ɢɡɭɱɟɧɢɟ ɤɭɥɶɬɭɪɵ CD34+ ɤɥɟɬɨɤ ɜ ɩɪɢɫɭɬɫɬɜɢɢ ɢ ɨɬɫɭɬɫɬɜɢɢ Jag1ɦɢɤɪɨɫɮɟɪ, ɱɬɨ ɨɛɟɳɚɟɬ ɩɨɥɭɱɟɧɢɟ ɢɧɮɨɪɦɚɰɢɢ ɨ ɛɟɥɤɚɯ, ɫɜɹɡɚɧɧɵɯ ɫ ɪɚɡɦɧɨɠɟɧɢɟɦ ɬɚɤɢɯ ɤɥɟɬɨɤ. ɉɪɨɬɟɨɦɢɤɚ, ɨɫɧɨɜɚɧɧɚɹ ɧɚ ɢɫɩɨɥɶɡɨɜɚɧɢɢ 2D/MALDI, ɬɪɟɛɭɟɬ ɢɫɩɨɥɶɡɨɜɚɧɢɹ ɞɨɫɬɚɬɨɱɧɨ ɛɨɥɶɲɢɯ ɨɛɴɟɦɨɜ ɛɟɥɤɚ ɜ ɢɫɫɥɟɞɭɟɦɵɯ ɨɛɪɚɡɰɚɯ. Ʉɚɤ ɭɠɟ ɭɤɚɡɵɜɚɥɨɫɶ, ɩɪɨɬɟɨɦɢɤɚ ɞɚɟɬ ɫɜɟɞɟɧɢɹ ɨ ɤɥɟɬɨɱɧɨɣ ɩɨɩɭɥɹɰɢɢ, ɚ ɧɟ ɨɛ ɨɬɞɟɥɶɧɵɯ ɤɥɟɬɤɚɯ. Ʉɨɧɬɪɨɥɢɪɭɹ ɢɡɦɟɧɟɧɢɹ ɜ ɛɟɥɤɚɯ, ɫ ɩɨɦɨɳɶɸ ɦɟɬɨɞɨɜ ɩɪɨɬɟɨɦɢɤɢ ɦɨɠɧɨ ɢɡɭɱɚɬɶ ɮɭɧɤɰɢɨɧɢɪɨɜɚɧɢɟ ɤɥɟɬɤɢ. ɗɬɢ ɢɡɦɟɧɟɧɢɟ ɦɨɠɧɨ ɢɧɞɭɰɢɪɨɜɚɬɶ, ɢɡɦɟɧɹɹ ɭɫɥɨɜɢɹ ɜ ɤɭɥɶɬɭɪɟ ɤɥɟɬɨɤ in vitro, ɜ ɱɚɫɬɧɨɫɬɢ, ɫɩɨɫɨɛɫɬɜɭɹ ɭɜɟɥɢɱɟɧɢɸ ɫɬɜɨɥɨɜɨɫɬɢ ɤɥɟɬɨɤ. Ɍɟɫɬɢɪɭɹ ɫɬɜɨɥɨɜɨɫɬɶ ɤɥɟɬɨɤ, ɦɵ ɩɨɥɭɱɚɟɦ ɫɩɨɫɨɛɧɨɫɬɶ ɨɛɧɚɪɭɠɢɜɚɬɶ ɤɥɸɱɟɜɵɟ ɛɟɥɤɢ, ɜɨɜɥɟɱɟɧɧɵɟ ɜ ɪɟɝɭɥɹɰɢɸ ɢ ɩɨɞɞɟɪɠɚɧɢɟ ɷɬɨɣ ɜɚɠɧɟɣɲɟɣ ɮɭɧɤɰɢɢ. ȽɋɄ ɨɛɵɱɧɨ ɤɭɥɶɬɢɜɢɪɭɸɬ in vitro ɜ ɤɨɦɛɢɧɚɰɢɢ ɫ ɪɚɡɥɢɱɧɵɦɢ ɮɚɤɬɨɪɚɦɢ ɪɨɫɬɚ, ɚ ɢɦɟɧɧɨ: ɮɚɤɬɨɪɨɦ ɫɬɜɨɥɨɜɵɯ ɤɥɟɬɨɤ (SCF, 100 ng/ml); ɥɢɝɚɧɞɨɦ Flt-3 (100 ng/ml); ɬɪɨɦɛɨɩɨɷɬɢɧɨɦ (TPO, 50 ng/ml); ɂɧɬɟɪɥɟɣɤɢɧɨɦ-6 (IL-6, 100 ng/ml). ɗɬɢ ɮɚɤɬɨɪɵ, ɤɚɤ ɛɵɥɨ ɩɨɤɚɡɚɧɨ, ɩɨɞɞɟɪɠɢɜɚɸɬ ɩɨɩɭɥɹɰɢɸ CD34+/CD38–ɤɥɟɬɨɤ, ɨɩɪɟɞɟɥɹɟɦɭɸ ɩɨ ɦɟɦɛɪɚɧɨɚɫɫɨɰɢɢɪɨɜɚɧɧɵɦ ɦɚɪɤɟɪɚɦ ɫɬɜɨɥɨɜɨɫɬɢ. ɗɬɚ ɩɨɩɭɥɹɰɢɹ ɫɬɜɨɥɨɜɵɯ ɤɥɟɬɨɤ ɦɨɠɟɬ ɛɵɬɶ ɞɨɩɨɥɧɢɬɟɥɶɧɨ ɫɬɢɦɭɥɢɪɨɜɚɧɚ ɩɪɢ ɢɫɩɨɥɶɡɨɜɚɧɢɢ ɫɢɧɬɟɬɢɱɟɫɤɨɝɨ ɚɝɟɧɬɚ, ɦɵɲɢɧɨɝɨ ɪɟɤɨɦɛɢɧɚɧɬɧɨɝɨ ɩɟɩɬɢɞɚ (Jagged-1), ɢɦɦɨɛɢɥɢɡɨɜɚɧɧɨɝɨ ɧɚ ɩɨɜɟɪɯɧɨɫɬɢ BrCN-aɤɬɢɜɢɪɨɜɚɧɧɵɯ ɦɢɤɪɨɫɮɟɪ. ɗɬɨɬ ɫɢɧɬɟɬɢɱɟɫɤɢɣ ɚɝɟɧɬ ɜɡɚɢɦɨɞɟɣɫɬɜɭɟɬ ɫ ɪɟɰɟɩɬɨɪɨɦ Notch-1, ɱɬɨ ɜɵɡɵɜɚɟɬ ɚɤɬɢɜɚɰɢɸ Notch-1-ɨɩɨɫɪɟɞɨɜɚɧɧɨɣ ɬɪɚɧɫɞɭɤɰɢɢ ɫɢɝɧɚɥɚ. ɉɨɥɚɝɚɸɬ, ɱɬɨ ɝɟɧɟɪɢɪɨɜɚɧɧɵɣ ɦɨɥɟɤɭɥɹɪɧɵɣ ɫɢɝɧɚɥ ɫɩɟɰɢɮɢɱɟɧ ɞɥɹ ɫɬɜɨɥɨɜɵɯ ɤɥɟɬɨɤ ɢ ɜɤɥɸɱɚɟɬ ɦɧɨɝɨɱɢɫɥɟɧɧɵɟ ɛɟɥɤɢ, ɧɟɨɛɯɨɞɢɦɵɟ ɞɥɹ 99 ɩɨɞɞɟɪɠɚɧɢɹ ɫɬɜɨɥɨɜɨɫɬɢ. Ɂɚ ɷɬɢɦɢ ɫɨɛɵɬɢɹɦɢ ɢ ɢɯ ɫɨɫɬɚɜɥɹɸɳɢɦɢ ɦɨɠɧɨ ɧɚɛɥɸɞɚɬɶ ɫ ɩɨɦɨɳɶɸ ɨɩɢɫɚɧɧɵɯ ɜ ɪɚɛɨɬɟ ɦɟɬɨɞɨɜ ɩɪɨɬɟɨɦɢɤɢ. ɉɨɬɟɧɰɢɚɥ ɩɪɨɬɟɨɦɢɤɢ ɫɜɹɡɵɜɚɸɬ ɫ ɬɳɚɬɟɥɶɧɵɦ ɨɩɢɫɚɧɢɟɦ ɛɟɥɤɨɜɨɝɨ ɩɪɨɮɢɥɹ ɤɥɟɬɨɱɧɵɯ ɩɨɩɭɥɹɰɢɣ. ɉɪɨɬɟɨɦɢɤɚ ɜɪɹɞ ɥɢ ɩɪɟɞɧɚɡɧɚɱɟɧɚ ɞɥɹ ɧɚɛɥɸɞɟɧɢɹ ɡɚ ɬɨɧɤɢɦɢ ɢɡɦɟɧɟɧɢɹɦɢ ɷɤɫɩɪɟɫɫɢɢ. Ȼɨɥɟɟ ɰɟɥɟɫɨɨɛɪɚɡɧɨ ɢɫɩɨɥɶɡɨɜɚɬɶ ɟɟ ɞɥɹ ɨɩɪɟɞɟɥɟɧɢɹ ɢ ɞɢɮɮɟɪɟɧɰɢɚɰɢɢ ɤɥɟɬɨɱɧɵɯ ɫɭɛɩɨɩɭɥɹɰɢɣ. ɂɫɬɢɧɧɵɟ ɜɨɡɦɨɠɧɨɫɬɢ ɩɪɨɬɟɨɦɢɤɢ, ɦɚɥɨɞɨɫɬɭɩɧɵɟ ɞɥɹ ɞɪɭɝɢɯ ɦɟɬɨɞɨɜ ɧɚɛɥɸɞɟɧɢɹ ɡɚ ɷɤɫɩɪɟɫɫɢɟɣ ɛɟɥɤɨɜ, ɡɚɤɥɸɱɚɸɬɫɹ ɜ ɨɛɧɚɪɭɠɟɧɢɢ ɩɨɫɬɬɪɚɧɫɥɹɰɢɨɧɧɵɯ ɦɨɞɢɮɢɤɚɰɢɣ (ɧɚɩɪɢɦɟɪ, ɮɨɫɮɨɪɢɥɢɪɨɜɚɧɢɹ). Ⱦɪɭɝɨɟ ɞɨɫɬɨɢɧɫɬɜɨ ɩɪɨɬɟɨɦɢɤɢ ɜ ɫɨɱɟɬɚɧɢɢ ɫ ɛɢɨɢɧɮɨɪɦɚɬɢɤɨɣ – ɫɩɨɫɨɛɧɨɫɬɶ ɢɡɭɱɚɬɶ ɤɥɟɬɤɭ ɢ ɤɚɤ ɰɟɥɨɟ, ɢ ɤɚɤ ɨɬɞɟɥɶɧɵɟ ɟɟ ɤɨɦɩɚɪɬɦɟɧɬɵ, ɮɢɤɫɢɪɨɜɚɬɶ ɢɡɦɟɧɟɧɢɹ ɜ ɧɢɯ ɤɨɧɰɟɧɬɪɚɰɢɢ ɛɟɥɤɨɜ. ɉɪɨɬɨɤɨɥ ɩɪɨɬɟɨɦɧɵɯ ɢɫɫɥɟɞɨɜɚɧɢɣ CD34+ ȽɋɄ ɛɵɥ ɚɜɬɨɦɚɬɢɡɢɪɨɜɚɧ ɧɚɦɢ ɫ ɰɟɥɶɸ ɦɚɤɫɢɦɚɥɶɧɨ ɜɨɡɦɨɠɧɨɝɨ ɩɨɜɵɲɟɧɢɹ ɜɨɫɩɪɨɢɡɜɨɞɢɦɨɫɬɢ ɢ ɢɫɤɥɸɱɟɧɢɹ ɨɲɢɛɨɱɧɨɝɨ ɜɥɢɹɧɢɹ ɱɟɥɨɜɟɱɟɫɤɨɝɨ ɮɚɤɬɨɪɚ. Ʉɥɸɱ ɤ ɤɚɪɬɢɪɨɜɚɧɢɸ ɜɫɟɝɨ ɩɪɨɬɟɨɦɚ ȽɋɄ ɥɟɠɚɬ ɜ ɚɜɬɨɦɚɬɢɡɚɰɢɢ ɩɪɨɬɨɤɨɥɚ ɬɚɤɢɦ ɨɛɪɚɡɨɦ, ɱɬɨ ɢɦɟɬɶ ɫɩɨɫɨɛɧɨɫɬɶ ɧɟ ɬɨɥɶɤɨ ɚɧɚɥɢɡɢɪɨɜɚɬɶ ɛɨɥɶɲɢɟ ɨɛɴɟɦɵ ɨɛɪɚɡɰɨɜ, ɧɨ ɢ ɩɨɞɞɟɪɠɢɜɚɬɶ ɜɵɫɨɤɢɣ ɭɪɨɜɟɧɶ ɢɫɩɨɥɧɟɧɢɹ ɨɩɟɪɚɰɢɣ ɧɚ ɩɪɨɬɹɠɟɧɢɢ ɜɫɟɯ ɫɬɚɞɢɣ ɚɧɚɥɢɡɚ. ɉɟɪɜɚɹ ɫɬɚɞɢɹ ɚɜɬɨɦɚɬɢɡɚɰɢɢ – ɢɡɜɥɟɱɟɧɢɟ ɛɟɥɤɨɜɵɯ ɩɹɬɟɧ ɢɡ ɝɟɥɹ. ɗɬɭ ɩɪɨɰɟɞɭɪɭ ɨɫɭɳɟɫɬɜɥɹɟɬ ɪɨɛɨɬ, ɜɵɪɟɡɚɸɳɢɣ ɩɹɬɧɨ ɥɟɡɜɢɟɦ ɞɢɚɦɟɬɪɨɦ 2 ɦɦ, ɜ ɨɬɥɢɱɢɟ ɨɬ ɪɭɱɧɨɝɨ ɫɩɨɫɨɛɚ ɫ ɢɫɩɨɥɶɡɨɜɚɧɢɟɦ ɫɤɚɥɶɩɟɥɹ. Ƚɥɚɜɧɨɟ ɩɪɟɢɦɭɳɟɫɬɜɨ ɚɜɬɨɦɚɬɢɡɚɰɢɢ ɜ ɞɚɧɧɨɦ ɫɥɭɱɚɟ – ɜɨɡɦɨɠɧɨɫɬɶ ɢɡɜɥɟɱɟɧɢɹ ɛɨɥɶɲɨɝɨ ɤɨɥɢɱɟɫɬɜɚ ɩɹɬɟɧ, ɱɬɨ ɡɚɬɪɭɞɧɢɬɟɥɶɧɨ ɫɞɟɥɚɬɶ ɜɪɭɱɧɭɸ. Ⱦɪɭɝɨɟ ɩɪɟɢɦɭɳɟɫɬɜɨ ɫɨɫɬɨɢɬ ɜ ɬɨɦ, ɱɬɨ ɜɵɪɟɡɚɧɢɟ ɩɪɨɢɫɯɨɞɢɬ ɜ ɡɨɧɟ ɧɚɢɛɨɥɶɲɟɣ ɤɨɧɰɟɧɬɪɚɰɢɢ ɛɟɥɤɚ, ɤɨɬɨɪɨɟ ɨɩɪɟɞɟɥɹɟɬɫɹ ɫ ɩɨɦɨɳɶɸ ɤɨɦɩɶɸɬɟɪɧɨɝɨ ɚɧɚɥɢɡɚ. ɗɬɨ ɩɨɡɜɨɥɹɟɬ 100 ɨɛɟɫɩɟɱɢɬɶ ɩɨɫɬɨɹɧɫɬɜɨ ɨɛɴɟɦɚ ɨɛɪɚɡɰɚ ɢ ɤɨɥɢɱɟɫɬɜɚ ɛɟɥɤɚ ɩɪɢ ɭɫɥɨɜɢɢ ɞɨɫɬɚɬɨɱɧɨɝɨ ɪɚɡɦɟɪɚ ɩɹɬɧɚ. ɉɪɢɦɟɧɟɧɢɟ ɥɟɡɜɢɹ ɬɚɤɠɟ ɫɩɨɫɨɛɫɬɜɭɟɬ ɧɟɪɚɡɪɭɲɟɧɢɸ ɫɨɫɟɞɧɢɯ ɩɹɬɟɧ. Ɍɟɦ ɧɟ ɦɟɧɟɟ, ɧɟɞɨɫɬɚɬɤɨɦ ɪɨɛɨɬɚ ɞɚɧɧɨɣ ɤɨɧɫɬɪɭɤɰɢɢ (Gelpix, Genetix) ɹɜɥɹɟɬɫɹ ɩɨɩɚɞɚɧɢɟ ɝɟɥɹ ɧɚ ɥɟɡɜɢɟ, ɱɬɨ ɡɚɬɪɭɞɧɹɟɬ ɢɡɜɥɟɱɟɧɢɟ ɩɨɫɥɟɞɭɸɳɢɯ ɛɟɥɤɨɜɵɯ ɩɹɬɟɧ. ɗɬɨ ɩɪɟɩɹɬɫɬɜɢɟ ɭɫɬɪɚɧɹɟɬɫɹ ɡɚ ɫɱɟɬ ɩɨɫɬɨɹɧɧɨɝɨ ɩɪɨɦɵɜɚɧɢɹ ɥɟɡɜɢɹ ɜɨɞɨɣ. ȼɬɨɪɚɹ ɚɜɬɨɦɚɬɢɡɢɪɨɜɚɧɧɚɹ ɫɬɚɞɢɹ – ɪɨɛɨɬɢɡɚɰɢɹ (GE healthcare) ɩɪɨɰɟɞɭɪɵ ɩɟɪɟɜɚɪɢɜɚɧɢɹ ɛɟɥɤɚ. Ɂɞɟɫɶ ɬɚɤɠɟ ɜɨɡɦɨɠɧɚ ɪɚɛɨɬɚ ɫ ɛɨɥɶɲɢɦ ɤɨɥɢɱɟɫɬɜɨɦ ɛɟɥɤɨɜɵɯ ɩɹɬɟɧ. Ɉɞɧɚ ɢɡ ɩɪɨɛɥɟɦ ɩɪɢ ɢɫɩɨɥɶɡɨɜɚɧɢɢ ɷɬɨɝɨ ɪɨɛɨɬɚ – ɫɨɫɤɚɥɶɡɵɜɚɧɢɟ ɝɟɥɹ ɫ ɥɟɡɜɢɹ, ɩɪɟɞɨɬɜɪɚɳɚɟɦɨɟ ɭɫɬɪɚɧɟɧɢɟɦ ɢɡɛɵɬɨɱɧɨɣ ɠɢɞɤɨɫɬɢ ɡɚ ɫɱɟɬ ɟɟ ɢɫɩɚɪɟɧɢɹ. Ɉɞɧɚɤɨ ɩɨɫɥɟɞɧɟɟ ɞɨɥɠɧɨ ɛɵɬɶ ɡɚɜɟɪɲɟɧɨ ɤ ɦɨɦɟɧɬɭ ɞɨɛɚɜɥɟɧɢɹ ɮɟɪɦɟɧɬɚ ɜɨ ɢɡɛɟɠɚɧɢɟ ɩɨɬɟɪɶ ɩɨɥɢɩɟɩɬɢɞɨɜ, ɚɞɫɨɪɛɢɪɭɸɳɢɯɫɹ ɧɚ ɩɥɚɫɬɢɤɨɜɵɯ ɫɬɟɧɤɚɯ ɫɨɫɭɞɚ. ɉɨɫɥɟɞɧɹɹ ɢ ɮɢɧɚɥɶɧɚɹ ɫɬɚɞɢɹ ɚɜɬɨɦɚɬɢɡɚɰɢɢ – ɢɫɩɨɥɶɡɨɜɚɧɢɟ ɪɨɛɨɬɚ Cartesian SynQuad, Genomic Solutions ɞɥɹ ɩɨɞɝɨɬɨɜɤɢ «ɫɷɧɞɜɢɱɚ» ɦɚɬɪɢɰɚ-ɨɛɪɚɡɟɰ (ɪɚɫɬɜɨɪ ɩɟɩɬɢɞɚ)-ɦɚɬɪɢɰɚ ɞɥɹ MADLI-ɚɧɚɥɢɡɚ. ɂɬɚɤ, ɧɚɦɢ ɩɪɨɞɟɦɨɧɫɬɪɢɪɨɜɚɧɨ, ɱɬɨ ɤɨɦɛɢɧɚɰɢɹ 2D ɷɥɟɤɬɪɨɮɨɪɟɡɚ ɫ ɮɪɚɤɰɢɨɧɢɪɨɜɚɧɢɟɦ ɤɥɟɬɨɱɧɵɯ ɨɪɝɚɧɟɥɥ ɦɨɠɟɬ ɞɚɬɶ ɢɧɮɨɪɦɚɰɢɸ ɨ ɜɧɭɬɪɢɤɥɟɬɨɱɧɨɣ ɥɨɤɚɥɢɡɚɰɢɢ ɫɩɟɰɢɮɢɱɟɫɤɢɯ ɛɟɥɤɨɜ. Ɋɚɡɪɚɛɨɬɚɧɧɵɣ ɦɟɬɨɞ ɨɬɥɢɱɚɟɬɫɹ ɜɨɫɩɪɨɢɡɜɨɞɢɦɨɫɬɶɸ ɢ ɜɨɡɦɨɠɧɨɫɬɶɸ ɤɨɥɢɱɟɫɬɜɟɧɧɨɣ ɨɰɟɧɤɢ ɪɟɡɭɥɶɬɚɬɨɜ. ȼɚɪɢɚɛɟɥɶɧɨɫɬɶ ɩɨɥɭɱɚɟɦɵɯ ɞɚɧɧɵɯ ɫɧɢɠɟɧɚ, ɜ ɬɨɦ ɱɢɫɥɟ ɡɚ ɫɱɟɬ ɦɢɧɢɦɢɡɚɰɢɢ ɩɨɦɟɯɨɨɛɪɚɡɨɜɚɧɢɹ ɫɨ ɫɬɨɪɨɧɵ ɞɨɦɢɧɢɪɭɸɳɢɯ ɜ ɨɛɪɚɡɰɟ ɛɟɥɤɨɜ. ȼ ɢɞɟɚɥɶɧɨɦ ɫɥɭɱɚɟ, ɞɨɥɠɧɚ ɛɵɬɶ ɜɨɡɦɨɠɧɨɫɬɶ ɚɜɬɨɦɚɬɢɡɚɰɢɢ ɜɫɟɝɨ ɧɚɛɨɪɚ ɩɪɨɰɟɞɭɪ. ɂɫɫɥɟɞɨɜɚɧɢɟ ȽɋɄ ɫ ɩɨɦɨɳɶɸ ɩɪɨɬɟɨɦɢɤɢ ɩɨɡɜɨɥɹɟɬ ɩɨɥɭɱɢɬɶ ɫɜɟɞɟɧɢɹ ɨ ɦɨɥɟɤɭɥɹɪɧɵɯ ɦɟɯɚɧɢɡɦɚɯ ɫɢɝɧɚɥɢɡɚɰɢɢ. ɇɚɩɪɢɦɟɪ, ɩɟɪɟ101 ɞɚɱɚ ɫɢɝɧɚɥɚ Notch1, ɤɨɬɨɪɵɣ ɚɤɬɢɜɢɪɭɟɬɫɹ Jag1 ɢ ɜɤɥɸɱɚɟɬ ɜ ɫɟɛɹ ɩɟɪɟɦɟɳɟɧɢɟ ɛɟɥɤɚ MAML1 ɢɡ ɰɢɬɨɩɥɚɡɦɵ ɜ ɹɞɪɨ, ɦɨɠɟɬ ɢɡɭɱɚɬɶɫɹ ɧɚ ɭɪɨɜɧɟ ɪɚɡɧɵɯ ɤɥɟɬɨɱɧɵɯ ɮɪɚɤɰɢɣ ɩɪɢ ɢɡɦɟɪɟɧɢɢ ɭɪɨɜɧɟɣ ɛɟɥɤɚ ɢ/ɢɥɢ ɷɤɫɩɪɟɫɫɢɢ ɧɨɜɵɯ ɛɟɥɤɨɜ. Ɍɚɤɢɦ ɨɛɪɚɡɨɦ, ɩɨɞɬɜɟɪɠɞɚɸɬɫɹ ɢɡɜɟɫɬɧɵɟ ɩɭɬɢ ɩɟɪɟɞɚɱɢ ɫɢɝɧɚɥɨɜ ɢɥɢ ɨɛɧɚɪɭɠɢɜɚɸɬɫɹ ɧɨɜɵɟ ɩɭɬɢ. Ȼɨɥɟɟ ɬɨɝɨ, ɞɥɹ ɢɡɜɟɫɬɧɵɯ ɩɭɬɟɣ ɩɟɪɟɞɚɱɢ ɫɢɝɧɚɥɚ ɦɨɝɭɬ ɛɵɬɶ ɪɚɫɫɱɢɬɚɧɵ ɬɟɨɪɟɬɢɱɟɫɤɢɟ ɡɧɚɱɟɧɢɹ pI ɢ MW ɛɟɥɤɨɜ-ɭɱɚɫɬɧɢɤɨɜ ɡɚ ɫɱɟɬ ɢɫɩɨɥɶɡɨɜɚɧɢɹ ɬɚɤɨɝɨ ɢɧɫɬɪɭɦɟɧɬɚ, ɤɚɤ «Compute pI/MW» (http://www.expasy.org/tools/). Ɋɚɫɫɱɢɬɚɧɧɵɟ ɬɚɤɢɦ ɨɛɪɚɡɨɦ pI ɢ MW ɞɥɹ MAML1 ɫɨɫɬɚɜɢɥɢ 8,45 ɢ 108 kDa ɫɨɨɬɜɟɬɫɬɜɟɧɧɨ. ɉɨ ɷɬɢɦ ɜɟɥɢɱɢɧɚɦ ɦɨɠɧɨ ɨɩɪɟɞɟɥɢɬɶ ɤɨɨɪɞɢɧɚɬɵ ɛɟɥɤɚ ɜ 2D-ɝɟɥɟ ɢ ɢɫɩɨɥɶɡɨɜɚɬɶ ɷɬɨ ɞɥɹ ɞɨɩɨɥɧɢɬɟɥɶɧɨɝɨ ɚɧɚɥɢɡɚ. ɏɨɬɹ ɬɚɤɨɣ ɩɨɞɯɨɞ ɢ ɢɦɟɟɬ ɨɩɪɟɞɟɥɟɧɧɵɟ ɧɟɞɨɫɬɚɬɤɢ, ɤɨɬɨɪɵɟ ɩɨɬɪɟɛɭɸɬ ɭɫɢɥɢɣ ɩɨ ɭɫɬɪɚɧɟɧɢɸ, ɨɧ ɧɚɫɬɨɥɶɤɨ ɩɪɟɜɨɫɯɨɞɢɬ ɬɪɚɞɢɰɢɨɧɧɵɟ ɦɟɬɨɞɢɤɢ, ɱɬɨ ɪɚɫɫɦɚɬɪɢɜɚɟɬɫɹ ɤɚɤ ɨɱɟɧɶ ɩɟɪɫɩɟɤɬɢɜɧɵɣ ɞɥɹ ɛɭɞɭɳɢɯ ɢɫɫɥɟɞɨɜɚɧɢɣ. Ɍɟɦ ɧɟ ɦɟɧɟɟ, ɢ ɬɪɚɞɢɰɢɨɧɧɵɟ ɦɟɬɨɞɵ ɢɫɫɥɟɞɨɜɚɧɢɹ ɩɪɨɬɟɨɦɚ ɤɥɟɬɨɱɧɨɣ ɩɨɩɭɥɹɰɢɢ ɧɟ ɢɫɱɟɪɩɚɥɢ ɫɜɨɢɯ ɜɨɡɦɨɠɧɨɫɬɟɣ ɞɥɹ ɢɡɭɱɟɧɢɹ ɫɬɜɨɥɨɜɵɯ ɤɥɟɬɨɤ. ȼ ɱɚɫɬɧɨɫɬɢ, ɨɧɢ ɦɨɝɭɬ ɛɵɬɶ ɢɫɩɨɥɶɡɨɜɚɧɵ ɞɥɹ ɥɭɱɲɟɝɨ ɩɨɧɢɦɚɧɢɹ ɦɨɥɟɤɭɥɹɪɧɨɣ ɫɢɝɧɚɥɢɡɚɰɢɢ ɢ ɜɡɚɢɦɨɞɟɣɫɬɜɢɹ ɛɟɥɤɨɜ ɞɪɭɝ ɫ ɞɪɭɝɨɦ. ȼ ɰɟɥɨɦ, ɜ ȽɋɄ ɧɚɦ ɭɞɚɥɨɫɶ ɢɞɟɧɬɢɮɢɰɢɪɨɜɚɬɶ ɛɨɥɟɟ 500 ɛɟɥɤɨɜ (ɩɪɟɞɫɬɚɜɥɟɧɵ ɜ ɩɪɢɥɨɠɟɧɢɢ), (ɜɤɥɸɱɚɹ ɢɡɨɮɨɪɦɵ ɢ ɩɨɫɬɬɪɚɧɫɥɹɰɢɨɧɧɵɟ ɦɨɞɢɮɢɤɚɰɢɢ), ɫɩɨɫɨɛɧɵɯ ɜɵɩɨɥɧɹɬɶ ɪɚɡɧɵɟ ɮɭɧɤɰɢɢ ɜ ɤɥɟɬɤɟ. ɉɨɥɭɱɟɧɧɚɹ ɩɪɨɬɟɨɦɧɚɹ ɤɚɪɬɚ ɹɜɥɹɟɬɫɹ ɩɨɥɟɡɧɵɦ ɢɧɫɬɪɭɦɟɧɬɨɦ, ɫɩɨɫɨɛɫɬɜɭɸɳɢɦ ɨɰɟɧɢɜɚɬɶ ɫɨɫɬɨɹɧɢɟ ɜ ɤɥɟɬɨɤ ɜ ɧɨɪɦɟ ɢ ɩɚɬɨɥɨɝɢɢ ɜ ɪɚɡɧɵɯ ɷɤɫɩɟɪɢɦɟɧɬɚɥɶɧɵɯ ɭɫɥɨɜɢɹɯ ɢ ɞɨɩɨɥɧɹɟɬ ɚɧɚɥɨɝɢɱɧɵɟ, ɪɚɧɟɟ ɩɨɥɭɱɟɧɧɵɟ ɞɚɧɧɵɟ [12, 40, 57, 65, 77, 91, 92, 106,109]. 102 4.3. ɉɪɨɬɟɨɦɢɤɚ ɚɬɟɪɨɫɤɥɟɪɨɡɚ ɢ ɩɟɪɫɩɟɤɬɢɜɵ ɢɫɩɨɥɶɡɨɜɚɧɢɹ ȽɋɄ ɞɥɹ ɬɟɪɚɩɢɢ ɚɬɟɪɨɫɤɥɟɪɨɡɚ ȼ ɰɟɥɹɯ ɥɭɱɲɟɣ ɢɧɬɟɪɩɪɟɬɚɰɢɢ ɪɟɡɭɥɶɬɚɬɨɜ, ɩɨɥɭɱɟɧɧɵɯ ɜ ɧɚɲɟɦ ɢɫɫɥɟɞɨɜɚɧɢɢ, ɩɪɟɞɫɬɚɜɥɹɟɬɫɹ ɰɟɥɟɫɨɨɛɪɚɡɧɵɦ ɜɡɹɬɶ ɡɚ ɨɫɧɨɜɭ ɨɞɧɭ ɢɡ ɤɨɧɰɟɩɰɢɣ ɪɚɡɜɢɬɢɹ ɚɬɟɪɨɫɤɥɟɪɨɡɚ ɨɬ ɧɚɱɚɥɶɧɵɯ ɫɬɚɞɢɣ ɞɨ ɫɨɫɬɨɹɧɢɹ ɜɵɪɚɠɟɧɧɨɣ ɩɚɬɨɥɨɝɢɢ. ȼ ɫɨɨɬɜɟɬɫɬɜɢɢ ɫ ɧɟɣ, ɤɨɦɩɥɟɤɫɧɚɹ ɫɢɫɬɟɦɚ ɪɟɩɚɪɚɰɢɢ ɚɪɬɟɪɢɣ ɜɤɥɸɱɚɟɬ ɤɚɤ ɥɨɤɚɥɶɧɵɟ, ɬɚɤ ɢ ɩɪɨɢɫɯɨɞɹɳɢɟ ɢɡ ɤɨɫɬɧɨɝɨ ɦɨɡɝɚ ɤɥɟɬɤɢ, ɨɛɟɫɩɟɱɢɜɚɸɳɢɟ ɝɨɦɟɨɫɬɚɡ ɢ ɰɟɥɨɫɬɧɨɫɬɶ ɫɨɫɭɞɨɜ. Ɂɚɜɢɫɹɳɢɣ ɨɬ ɜɨɡɪɚɫɬɚ ɨɬɤɚɡ ɤɨɫɬɧɨɝɨ ɦɨɡɝɚ ɩɪɨɞɭɰɢɪɨɜɚɬɶ ɫɨɫɭɞɢɫɬɵɟ ɩɪɨɝɟɧɢɬɨɪɧɵɟ ɤɥɟɬɤɢ, ɨɬɜɟɬɫɬɜɟɧɧɵɟ ɡɚ ɜɨɫɫɬɚɧɨɜɥɟɧɢɟ ɚɪɬɟɪɢɣ – ɧɟɫɩɨɫɨɛɧɨɫɬɶ, ɤɨɬɨɪɚɹ ɜɵɡɜɚɧɚ ɞɥɹɳɢɦɢɫɹ ɜ ɬɟɱɟɧɢɟ ɜɫɟɣ ɠɢɡɧɢ ɮɚɤɬɨɪɚɦɢ, ɬɚɤɢɦɢ, ɤɚɤ ɝɢɩɟɪɥɢɩɢɞɟɦɢɹ, ɫɩɨɫɨɛɫɬɜɭɟɬ ɪɚɡɜɢɬɢɸ ɚɬɟɪɨɫɤɥɟɪɨɡɚ ɢ ɟɝɨ ɬɪɨɦɛɨɷɦɛɨɥɢɱɟɫɤɢɯ ɨɫɥɨɠɧɟɧɢɣ. Ʉɚɤ ɩɨɫɥɟɞɫɬɜɢɟ ɬɚɤɨɝɨ ɨɬɤɚɡɚ, ɧɨɪɦɚɥɶɧɵɣ ɩɪɨɰɟɫɫ ɜɨɫɫɬɚɧɨɜɥɟɧɢɹ ɚɪɬɟɪɢɚɥɶɧɨɣ ɫɬɟɧɤɢ ɧɚɪɭɲɚɟɬɫɹ. ɇɚɪɭɲɟɧɢɟ ɪɚɜɧɨɜɟɫɢɹ ɦɟɠɞɭ ɩɨɜɪɟɠɞɟɧɢɟɦ ɚɪɬɟɪɢɚɥɶɧɨɣ ɫɬɟɧɤɢ ɢ ɟɟ ɜɨɫɫɬɚɧɨɜɥɟɧɢɟɦ ɜɟɞɟɬ ɤ ɚɬɟɪɨɫɤɥɟɪɨɬɢɱɟɫɤɨɦɭ ɜɨɫɩɚɥɟɧɢɸ ɢ ɩɨɫɥɟɞɭɸɳɢɦ ɨɫɥɨɠɧɟɧɢɹɦ. Ʉɨɫɬɧɵɣ ɦɨɡɝ ɢ ɩɪɨɢɫɯɨɞɹɳɢɟ ɢɡ ɧɟɝɨ ɋɄ ɩɪɟɞɫɬɚɜɥɹɸɬ ɫɨɛɨɣ ɤɥɸɱɟɜɵɟ ɪɟɝɭɥɹɬɨɪɵ ɚɬɟɪɨɫɤɥɟɪɨɡɚ, ɢ ɩɪɨɝɪɟɫɫ ɜ ɩɪɟɞɨɬɜɪɚɳɟɧɢɢ ɢ ɥɟɱɟɧɢɢ ɚɬɟɪɨɫɤɥɟɪɨɡɚ ɢ ɟɝɨ ɬɪɨɦɛɨɷɦɛɨɥɢɱɟɫɤɢɯ ɨɫɥɨɠɧɟɧɢɣ ɞɨɥɠɟɧ ɨɫɭɳɟɫɬɜɥɹɬɶɫɹ ɫ ɭɱɟɬɨɦ ɷɬɨɝɨ ɢɡɦɟɪɟɧɢɹ ɩɪɨɰɟɫɫɚ ɛɨɥɟɡɧɢ [19]. Ȼɟɥɤɢ ɋɄ, ɰɢɪɤɭɥɢɪɭɸɳɢɯ ɜ ɤɪɨɜɢ, ɦɨɝɭɬ ɫɥɭɠɢɬɶ ɢ ɞɢɚɝɧɨɫɬɢɱɟɫɤɢɦɢ ɦɚɪɤɟɪɚɦɢ ɞɥɹ ɩɪɟɞɫɤɚɡɚɧɢɹ ɨɬɧɨɫɢɬɟɥɶɧɨɝɨ ɪɢɫɤɚ ɪɚɡɜɢɬɢɹ ɚɬɟɪɨɫɤɥɟɪɨɡɚ, ɢ ɢɫɬɨɱɧɢɤɨɦ ɢɧɮɨɪɦɚɰɢɢ ɨ ɪɟɝɟɧɟɪɚɬɢɜɧɨɦ ɩɨɬɟɧɰɢɚɥɟ ɨɪɝɚɧɢɡɦɚ. 103 Ɍɚɤɢɦ ɨɛɪɚɡɨɦ, ɢɡɭɱɟɧɢɟ ɩɪɨɬɟɨɦɧɵɯ ɩɪɨɮɢɥɟɣ ɤɚɤ ɜɧɭɬɪɟɧɧɢɯ ɫɬɟɧɨɤ ɫɨɫɭɞɨɜ, ɬɚɤ ɢ ȽɋɄ ɫɩɨɫɨɛɧɨ ɩɪɢɜɟɫɬɢ, ɜ ɩɟɪɫɩɟɤɬɢɜɟ, ɤ ɰɟɥɟɧɚɩɪɚɜɥɟɧɧɨɣ ɩɪɨɮɢɥɚɤɬɢɤɟ ɢ ɬɟɪɚɩɢɢ ɚɬɟɪɨɫɤɥɟɪɨɡɚ ɫ ɩɨɦɨɳɶɸ ɫɬɜɨɥɨɜɵɯ ɤɥɟɬɨɤ. ɉɪɢ ɷɬɨɦ ɰɟɥɟɫɨɨɛɪɚɡɧɨ, ɜɢɞɢɦɨ, ɩɪɢɧɹɬɶ ɜɨ ɜɧɢɦɚɧɢɟ ɫɟɤɪɟɬɨɪɧɵɟ ɮɚɤɬɨɪɵ, ɫɩɨɫɨɛɧɵɟ ɩɨɜɥɹɬɶ ɧɚ ɪɚɡɜɢɬɢɟ ɢ ɜɵɠɢɜɚɧɢɟ ɋɄ. ɋɟɤɪɟɬɢɪɭɟɦɵɟ ɛɟɥɤɢ, ɤɚɤ ɢɡɜɟɫɬɧɨ, ɨɩɪɟɞɟɥɹɸɬ ɜ ɡɧɚɱɢɬɟɥɶɧɨɣ ɫɬɟɩɟɧɢ ɝɨɦɟɨɫɬɚɡ ɢ ɤɨɦɦɭɧɢɤɚɰɢɢ ɜɧɭɬɪɢ ɤɚɪɞɢɨɜɚɫɤɭɥɹɪɧɨɣ ɫɢɫɬɟɦɵ ɜ ɨɬɜɟɬ ɧɚ ɟɟ ɩɨɪɚɠɟɧɢɟ. ȼɚɠɧɭɸ ɪɨɥɶ ɢɝɪɚɸɬ ɢ ɩɨɜɟɪɯɧɨɫɬɧɵɟ ɛɟɥɤɢ ɋɄ. ɂɫɫɥɟɞɨɜɚɧɢɟ ɩɪɨɬɟɨɦɚ ɷɥɟɦɟɧɬɨɜ ɋɋɋ, ɚɬɟɪɨɫɤɥɟɪɨɬɢɱɟɫɤɢɟ ɢɡɦɟɧɟɧɢɹ ɜ ɤɨɬɨɪɨɣ ɡɚɬɪɚɝɢɜɚɸɬ ɦɧɨɝɢɟ ɟɟ ɤɨɦɩɨɧɟɧɬɵ, ɜɤɥɸɱɚɹ ɝɥɚɞɤɨɦɵɲɟɱɧɵɟ ɢ ɷɧɞɨɬɟɥɢɚɥɶɧɵɟ ɤɥɟɬɤɢ, ɭɠɟ ɩɪɢɜɥɟɤɚɟɬ ɜɧɢɦɚɧɢɟ ɪɹɞɚ ɭɱɟɧɵɯ. Ⱥɜɬɨɪɵ ɷɬɢɯ ɪɚɛɨɬ ɩɨɥɚɝɚɸɬ, ɱɬɨ ɜɵɹɜɥɟɧɢɟ ɦɨɞɢɮɢɰɢɪɭɟɦɵɯ ɩɚɬɨɥɨɝɢɟɣ ɛɟɥɤɨɜ ɦɨɠɟɬ ɞɚɬɶ ɤɥɸɱ ɤɚɤ ɤ ɩɨɧɢɦɚɧɢɸ ɦɟɯɚɧɢɡɦɨɜ ɚɬɟɪɨɫɤɥɟɪɡɚ, ɬɚɤ ɢ ɤ ɟɝɨ ɥɟɱɟɧɢɸ. ȼ ɞɚɧɧɵɣ ɦɨɦɟɧɬ ɬɚɤɢɯ ɷɤɫɩɟɪɢɦɟɧɬɨɜ, ɯɚɪɚɤɬɟɪɢɡɭɟɦɵɯ ɤɚɤ «ɮɭɧɤɰɢɨɧɚɥɶɧɚɹ ɩɪɨɬɟɨɦɢɤɚ», ɜɵɩɨɥɧɟɧɨ ɹɜɧɨ ɧɟɞɨɫɬɚɬɨɱɧɨ. Ɍɟɦ ɧɟ ɦɟɧɟɟ, ɫɨɨɬɜɟɬɫɬɜɭɸɳɟɟ ɩɨɜɟɞɟɧɢɟ ɛɟɥɤɨɜ, ɜɤɥɸɱɚɹ ɢɡɦɟɧɟɧɢɟ ɢɯ ɤɨɥɢɱɟɫɬɜɚ, ɢɡɭɱɚɥɨɫɶ ɩɪɢ ɤɚɪɞɢɨɦɢɨɩɚɬɢɹɯ ɱɟɥɨɜɟɤɚ ɢ ɠɢɜɨɬɧɵɯ ɢ ɜ ɪɹɞɟ ɞɪɭɝɢɯ ɫɥɭɱɚɟɜ. ɋɨɝɥɚɫɧɨ ɩɪɟɞɜɚɪɢɬɟɥɶɧɵɦ ɞɚɧɧɵɦ, ɧɚɢɛɨɥɟɟ ɨɛɟɳɚɸɳɢɦɢ ɦɚɪɤɟɪɚɦɢ ɞɥɹ ɤɚɪɞɢɨɩɪɨɬɟɨɦɢɤɢ ɦɨɝɭɬ ɛɵɬɶ ɬɪɨɩɨɧɢɧɵ, ɢɡɨɮɨɪɦɵ ɚɥɶɮɚ-1- ɮɢɛɪɢɧɨɝɟɧɚ, ɢɡɨɮɨɪɦɵ ɚɩɨɥɢɩɨɩɪɨɬɟɢɧɚ Ⱥ-1, ɋ-ɪɟɚɤɬɢɜɧɵɣ ɛɟɥɨɤ ɢ ɞɪ. [1,10,16,30]. Ƚɥɚɜɧɨɟ ɩɪɟɩɹɬɫɬɜɢɟ ɞɥɹ ɚɧɚɥɢɡɚ ɩɪɨɬɟɨɦɚ ɫɨɫɭɞɨɜ ɩɪɢ ɚɬɟɪɨɝɟɧɟɡɟ – ɝɟɬɟɪɨɝɟɧɧɨɫɬɶ ɤɥɟɬɨɱɧɨɝɨ ɫɨɫɬɚɜɚ ɚɬɟɪɨɫɤɥɟɪɨɬɢɱɟɫɤɢɯ ɛɥɹɲɟɤ. Ⱦɪɭɝɨɣ ɦɟɬɨɞɢɱɟɫɤɨɣ ɩɪɨɛɥɟɦɨɣ ɹɜɥɹɟɬɫɹ ɜɵɛɨɪ ɚɞɟɤɜɚɬɧɨɝɨ ɤɨɧɬɪɨɥɹ, ɫ ɚɤɰɟɧɬɨɦ ɧɚ ɥɨɤɚɥɢɡɚɰɢɸ ɨɛɪɚɡɰɨɜ ɜ ɫɨɫɭɞɢɫɬɨɣ ɫɬɟɧɤɟ ɢ ɨɬɫɭɬɫɬɜɢɟ ɩɪɨɬɟɨɥɢɬɢɱɟɫɤɢɯ ɢɡɦɟɧɟɧɢɣ ɞɨ ɧɚɱɚɥɚ ɚɧɚɥɢɡɚ. ɋ ɭɱɟɬɨɦ 104 ɜɨɫɩɚɥɢɬɟɥɶɧɨɣ ɩɪɢɪɨɞɵ ɚɬɟɪɨɫɤɥɟɪɨɡɚ, ɫɥɟɞɭɟɬ ɩɪɢɧɢɦɚɬɶ ɜɨ ɜɧɢɦɚɧɢɟ ɬɚɤɠɟ ɜɡɚɢɦɨɞɟɣɫɬɜɢɟ ɦɟɠɞɭ ɢɧɮɢɥɶɬɪɨɜɚɧɧɵɦɢ Ɍ-ɥɢɦɮɨɰɢɬɚɦɢ ɢ ɦɚɤɪɨɮɚɝɚɦɢ, ɨɛɪɚɡɨɜɚɧɧɵɦɢ ɢɡ ɦɨɧɨɰɢɬɨɜ. Ɇɚɤɪɨɮɚɝɢ ɞɨɜɨɥɶɧɨ ɦɧɨɝɨɱɢɫɥɟɧɧɵ ɢ ɦɨɝɭɬ ɦɚɫɤɢɪɨɜɚɬɶ ɛɟɥɤɢ, ɩɪɨɢɫɯɨɞɹɳɢɟ ɢɡ ɤɨɦɩɨɧɟɧɬɨɜ ɧɨɪɦɚɥɶɧɨɣ ɫɬɟɧɤɢ ɫɨɫɭɞɨɜ. Ȼɨɥɟɟ ɬɨɝɨ, ɨɛɧɚɪɭɠɟɧɧɨɟ ɭɜɟɥɢɱɟɧɢɟ ɤɨɥɢɱɟɫɬɜɚ ɤɚɤɨɝɨ-ɥɢɛɨ ɛɟɥɤɚ ɦɨɠɟɬ ɹɜɥɹɬɶɫɹ ɪɟɡɭɥɶɬɚɬɨɦ ɢɧɮɢɥɶɬɪɚɰɢɢ ɦɨɧɨɰɢɬɨɜ ɜ ɩɨɪɚɠɟɧɧɭɸ ɚɪɬɟɪɢɸ. ɇɟɫɦɨɬɪɹ ɧɚ ɷɬɢ ɨɝɪɚɧɢɱɟɧɢɹ, ɩɟɪɜɵɟ ɩɨɩɵɬɤɢ ɚɧɚɥɢɡɚ ɚɬɟɪɨɫɤɥɟɪɨɬɢɱɟɫɤɨɝɨ ɩɨɪɚɠɟɧɢɹ ɫ ɩɨɦɨɳɶɸ 2-D ɛɵɥɢ ɩɪɟɞɩɪɢɧɹɬɵ ɩɨɱɬɢ 20 ɥɟɬ ɧɚɡɚɞ. Ɍɚɤ, Stastny et al. [81] ɫɪɚɜɧɢɜɚɥ ɛɟɥɤɨɜɵɣ ɫɨɫɬɚɜ ɥɢɩɨɮɢɛɪɨɡɧɨɣ ɛɥɹɲɤɢ ɫ ɫɨɫɬɚɜɨɦ ɧɨɪɦɚɥɶɧɨɣ ɢɧɬɢɦɵ ɢ ɨɛɧɚɪɭɠɢɥ, ɱɬɨ ɛɟɥɤɢ ɩɥɚɡɦɟɧɧɨɝɨ ɩɪɨɢɫɯɨɠɞɟɧɢɹ (ɚɥɶɛɭɦɢɧ, ɮɢɛɪɢɧɨɝɟɧ, ɢɦɦɭɧɨɝɥɨɛɭɥɢɧ G, a-1 ɚɧɬɢɬɪɢɩɫɢɧ, ɬɪɚɧɫɮɟɪɪɢɧ, ɝɚɩɬɨɝɥɨɛɢɧ, Ⱥɩo A-I, and Ⱥɩo A-II) ɚɤɤɭɦɭɥɢɪɭɸɬɫɹ ɜ ɩɨɪɚɠɟɧɧɵɯ ɫɨɫɭɞɚɯ. Ⱥɧɚɥɨɝɢɱɧɨ, Song et al. [79] ɨɛɧɚɪɭɠɢɥ, ɱɬɨ ɛɟɥɤɢ ɢɡ ɩɥɚɡɦɵ ɫɬɚɧɨɜɹɬɫɹ ɛɨɥɟɟ ɦɧɨɝɨɱɢɫɥɟɧɧɵ ɜ ɢɧɬɢɦɟ ɚɪɬɟɪɢɣ ɩɪɢ ɫɬɚɪɟɧɢɢ ɨɞɧɨɜɪɟɦɟɧɧɨ ɫ ɭɬɨɥɳɟɧɢɟɦ ɢɧɬɢɦɵ. ɍɫɬɚɧɨɜɥɟɧɨ, ɱɬɨ ɨɫɬɟɨɧɟɤɬɢɧ ɭɫɢɥɟɧɧɨ ɷɤɫɩɪɟɫɫɢɪɭɟɬɫɹ ɤɥɟɬɤɚɦɢ, ɩɪɢɫɭɬɫɬɜɭɸɳɢɦɢ ɜ ɫɬɟɧɤɟ ɫɨɫɭɞɚ ɩɪɢ ɩɪɨɝɪɟɫɫɢɪɨɜɚɧɢɢ ɚɬɟɪɨɫɤɥɟɪɨɡɚ, ɚ ɢɦɟɧɧɨ ɩɪɢ ɤɚɥɶɰɢɮɢɤɚɰɢɢ ɚɬɟɪɨɫɤɥɟɪɨɬɢɱɟɫɤɨɣ ɛɥɹɲɤɢ [28]. ȼ ɛɨɥɟɟ ɩɨɡɞɧɢɯ ɪɚɛɨɬɚɯ ɫ ɩɨɦɨɳɶɸ ɥɚɡɟɪɧɨɣ ɞɟɧɫɢɬɨɦɟɬɪɢɢ ɛɵɥɨ ɩɨɞɬɜɟɪɠɞɟɧɨ ɡɧɚɱɢɬɟɥɶɧɨɟ ɭɜɟɥɢɱɟɧɢɟ ɨɬɧɨɲɟɧɢɹ ɚɥɶɛɭɦɢɧ/ɚɤɬɢɧ ɜ ɠɢɪɨɜɵɯ ɩɨɥɨɫɚɯ ɩɨ ɫɪɚɜɧɟɧɢɸ ɫ ɧɨɪɦɨɣ [83]. ɉɪɢ ɫɪɚɜɧɟɧɢɢ ɚɬɟɪɨɫɤɥɟɪɨɬɢɱɟɫɤɢɯ ɛɥɹɲɟɤ ɤɨɪɨɧɚɪɧɵɯ ɚɪɬɟɪɢɣ ɫ ɧɨɪɦɚɥɶɧɵɦɢ ɤɨɪɨɧɚɪɧɵɦɢ ɚɪɬɟɪɢɹɦɢ You ɩɪɨɞɟɦɨɧɫɬɪɢɪɨɜɚɥ ɭɜɟɥɢɱɟɧɢɟ ɷɤɫɩɪɟɫɫɢɢ ɮɟɪɪɢɬɢɧɚ (ɛɟɥɤɚ, ɭɱɚɫɬɜɭɸɳɟɝɨ ɜ ɤɥɟɬɨɱɧɨɦ ɧɚɤɨɩɥɟɧɢɢ ɠɟɥɟɡɚ) ɜ ɤɨɪɨɧɚɪɧɵɯ ɚɪɬɟɪɢɹɯ ɢɧɞɢɜɢɞɨɜ ɫ ɡɚɛɨɥɟɜɚɧɢɹɦɢ ɤɨɪɨɧɚɪ105 ɧɵɯ ɚɪɬɟɪɢɣ [104]. ȼ ɝɨɦɨɝɟɧɚɬɚɯ ɚɬɟɪɨɫɤɥɟɪɨɬɢɱɟɫɤɢɯ ɛɥɹɲɟɤ ɱɟɥɨɜɟɤɚ ɨɛɧɚɪɭɠɟɧɨ 2-ɤɪɚɬɧɨɟ ɭɜɟɥɢɱɟɧɢɟ ɥɟɝɤɨɰɟɩɨɱɟɱɧɨɝɨ ɮɟɪɪɢɬɢɧɚ ɩɨ ɫɪɚɜɧɟɧɢɸ ɫ ɤɨɧɬɪɨɥɟɦ. ɉɪɟɞɩɨɥɚɝɚɟɬɫɹ ɭɱɚɫɬɢɟ ɷɬɨɝɨ ɛɟɥɤɚ ɜ ɨɛɪɚɡɨɜɚɧɢɢ ɚɤɬɢɜɧɵɯ ɮɨɪɦ ɤɢɫɥɨɪɨɞɚ, ɜɵɡɵɜɚɸɳɢɯ ɨɤɢɫɥɟɧɢɟ ɥɢɩɢɞɨɜ ɜ ɫɬɟɧɤɟ ɤɨɪɨɧɚɪɧɵɯ ɚɪɬɟɪɢɣ. ȼ ɧɟɫɬɚɛɢɥɶɧɵɯ ɛɥɹɲɤɚɯ (ɩɨɫɥɟɞɧɢɟ ɫɬɚɞɢɢ ɪɚɡɜɢɬɢɹ) ɨɛɧɚɪɭɠɟɧɵ ɬɚɤɠɟ ɢɡɨɮɨɪɦɵ Į1-ɚɧɬɢɬɪɢɩɫɢɧɚ [55] ɢ ɧɚɛɨɪɚ ɢɡ 27 ɛɟɥɤɨɜ, ɭɱɚɫɬɜɭɸɳɢɯ ɜ ɛɢɨɥɨɝɢɱɟɫɤɢɯ ɩɪɨɰɟɫɫɚɯ (ɦɢɝɪɚɰɢɢ ɝɥɚɞɤɨɦɵɲɟɱɧɵɯ ɤɥɟɬɨɤ, ɚɤɬɢɜɚɰɢɢ ɦɟɬɚɥɥɨɩɪɨɬɟɢɧɚɡ ɦɚɬɪɢɤɫɚ, ɪɟɝɭɥɹɰɢɢ ɩɪɨɜɨɫɩɚɥɢɬɟɥɶɧɵɯ ɰɢɬɨɤɢɧɨɜ). ȼ ɨɬɥɢɱɢɟ ɨɬ ɜɵɹɫɧɟɧɢɹ ɪɨɥɢ ɨɬɞɟɥɶɧɵɯ ɛɟɥɤɨɜ ɜ ɪɚɡɜɢɬɢɢ ɚɬɟɪɨɫɤɥɟɪɨɡɚ, ɩɪɨɬɟɨɦɢɤɚ ɩɨɡɜɨɥɹɟɬ ɨɰɟɧɢɬɶ ɦɢɤɪɨɨɤɪɭɠɟɧɢɟ ɛɥɹɲɤɢ ɜ ɰɟɥɨɦ. Ɍɚɤ, ɨɛɧɚɪɭɠɟɧɨ ɫɧɢɠɟɧɢɟ ɛɟɥɤɚ ɬɟɩɥɨɜɨɝɨ ɲɨɤɚ (hsp27) ɜ ɫɭɩɟɪɧɚɬɚɧɬɟ ɤɭɥɶɬɭɪɵ ɩɨɪɚɠɟɧɧɵɯ ɚɬɟɪɨɫɤɥɟɪɨɡɨɦ ɤɥɟɬɨɤ, ɚ ɬɚɤɠɟ hsp27, hsp20, ɫɭɩɟɪɨɤɫɢɞɞɢɫɦɭɬɚɡɵ 3 ɜ ɫɬɚɛɢɥɶɧɵɯ ɛɥɹɲɤɚɯ ɩɨ ɫɪɚɜɧɟɧɢɸ ɫ ɧɟɫɬɚɛɢɥɶɧɵɦɢ [63]. ɇɚɤɨɧɟɰ, ɫɥɟɞɭɟɬ ɭɤɚɡɚɬɶ ɧɚ ɪɚɛɨɬɭ, ɜ ɤɨɬɨɪɨɣ ɢɡɭɱɚɥɢɫɶ ɛɟɥɤɢ ɢɡ ɢɦɦɭɧɨɝɢɫɬɨɯɢɦɢɱɟɫɤɢ ɤɥɚɫɫɢɮɢɰɢɪɨɜɚɧɧɵɯ ɫɬɚɛɢɥɶɧɵɯ ɢ ɧɟɫɬɚɛɢɥɶɧɵɯ ɛɥɹɲɟɤ ɫɨɧɧɵɯ ɚɪɬɟɪɢɣ [60]. Ⱥɜɬɨɪɵ ɨɛɧɚɪɭɠɢɥɢ, ɱɬɨ ɨɤɨɥɨ 70% ɢɞɟɧɬɢɮɢɰɢɪɨɜɚɧɧɵɯ ɛɟɥɤɨɜ ɩɪɨɢɫɯɨɞɹɬ ɢɡ ɩɥɚɡɦɵ, ɱɬɨ ɫɜɢɞɟɬɟɥɶɫɬɜɭɟɬ ɨ ɧɚɪɭɲɟɧɢɢ ɛɚɪɶɟɪɧɵɯ ɮɭɧɤɰɢɣ ɷɧɞɨɬɟɥɢɹ ɧɟɡɚɜɢɫɢɦɨ ɨɬ ɬɢɩɚ ɛɥɹɲɤɢ. ȼ ɧɟɫɬɚɛɢɥɶɧɵɯ ɛɥɹɲɤɚɯ, ɩɨ ɫɪɚɜɧɟɧɢɸ ɫɨ ɫɬɚɛɢɥɶɧɵɦɢ, ɫɧɢɠɚɥɨɫɶ ɫɨɞɟɪɠɚɧɢɟ ɫɭɩɟɪɨɤɫɢɞɞɢɫɦɭɬɚɡɵ 3 (ɋɈȾ 3) ɢ ɝɥɸɬɚɬɢɨɧ s-ɬɪɚɧɫɮɟɪɚɡɵ (ȽɋɌ), ɛɟɥɤɨɜ ɬɟɩɥɨɜɨɝɨ ɲɨɤɚ 20 ɢ 27, ɚɧɧɟɤɫɢɧɚ Ⱥ10, ɚ ɜɨɡɪɚɫɬɚɥɨ ɫɨɞɟɪɠɚɧɢɟ ɥɟɝɤɨɝɨ ɮɟɪɪɢɬɢɧɚ, ɋɈȾ 2 ɢ ɮɪɚɝɦɟɧɬɚ D ɮɢɛɪɢɧɨɝɟɧɚ. Ʉɚɤ ɢɡɜɟɫɬɧɨ, ɜɫɟ ɷɬɢ ɛɟɥɤɢ ɬɚɤ ɢɥɢ ɢɧɚɱɟ ɜɨɜɥɟɱɟɧɵ ɜ ɨɤɢɫɥɢɬɟɥɶɧɵɟ ɢɥɢ ɜɨɫɩɚɥɢɬɟɥɶɧɵɟ ɩɪɨɰɟɫɫɵ, ɚ ɬɚɤɠɟ ɨɛɪɚɡɨɜɚɧɢɟ ɛɥɹɲɟɤ. 106 Ⱥɥɶɬɟɪɧɚɬɢɜɧɵɣ ɩɨɞɯɨɞ ɤ ɢɫɫɥɟɞɨɜɚɧɢɸ ɩɪɨɬɟɨɦɚ ɛɥɹɲɤɢ ɩɪɢɦɟɧɢɥ Duran and Mas et al. [29]. ȼ ɷɬɢɯ ɨɩɵɬɚɯ ɨɛɪɚɡɰɵ ɢɡ ɫɨɧɧɵɯ ɚɪɬɟɪɢɣ ɤɭɥɶɬɢɜɢɪɨɜɚɥɢ ɜ ɛɟɡɛɟɥɤɨɜɨɣ ɫɪɟɞɟ ɢ ɚɧɚɥɢɡɢɪɨɜɚɥɢ ɫɭɩɟɪɧɚɬɚɧɬ ɫ ɩɨɦɨɳɶɸ 2-DE. ɍɫɬɚɧɨɜɥɟɧɨ, ɱɬɨ ɛɟɥɤɢ, ɜɵɫɜɨɛɨɠɞɚɟɦɵɟ ɢɡ ɛɥɹɲɟɤ, ɜɨɜɥɟɱɟɧɵ ɜ ɨɛɪɚɬɧɵɣ ɬɪɚɧɫɩɨɪɬ ɯɨɥɟɫɬɟɪɢɧɚ (ɚɩɨɥɢɩɨɩɪɨɬɟɢɧ ȼ-100, ɚɩɨɥɢɩɨɩɪɨɬɟɢɧ Ⱥ-1), ɚɩɨɩɬɨɡ (ɥɟɤɬɢɧ, ɪɚɫɬɜɨɪɹɟɦɵɣ b-ɝɚɥɚɤɬɨɡɢɞɚɡɨɣ), ɞɟɝɪɚɞɚɰɢɸ ɛɟɥɤɨɜ (ɝɢɞɪɨɥɚɡɚ 23) ɢ ɚɧɬɢɨɤɢɫɥɢɬɟɥɶɧɨɟ ɞɟɣɫɬɜɢɟ (ɫɭɩɟɪɨɤɫɢɞɞɢɫɦɭɬɚɡɚ, ɩɟɪɨɤɫɢɪɟɞɨɤɫɢɧ 2). ɋ ɩɨɜɵɲɟɧɢɟɦ ɫɥɨɠɧɨɫɬɢ ɩɨɪɚɠɟɧɢɹ ɜɨɡɪɚɫɬɚɥɨ ɢ ɤɨɥɢɱɟɫɬɜɨ ɛɟɥɤɨɜ. Ɉɞɧɚɤɨ ɧɟɹɫɧɨ, ɜɵɞɟɥɹɸɬɫɹ ɥɢ ɷɬɢ ɛɟɥɤɢ ɢɡ ɛɥɹɲɟɤ ɚɤɬɢɜɧɨ ɢɥɢ ɩɚɫɫɢɜɧɚɹ ɞɢɮɮɭɡɢɹ ɜ ɫɪɟɞɭ ɤɥɟɬɨɱɧɨɣ ɤɭɥɶɬɭɪɵ ɩɪɨɢɫɯɨɞɢɬ ɥɟɝɱɟ ɢɡ ɛɥɹɲɟɤ, ɱɟɦ ɢɡ ɧɨɪɦɚɥɶɧɵɯ ɚɪɬɟɪɢɣ. Ȼɟɥɨɤ ɬɟɩɥɨɜɨɝɨ ɲɨɤɚ 27, ɫɟɤɪɟɬɢɪɭɟɦɵɣ ɢɡ ɛɥɹɲɤɢ ɜ ɤɭɥɶɬɭɪɚɥɶɧɭɸ ɫɪɟɞɭ, ɪɚɫɫɦɚɬɪɢɜɚɟɬɫɹ ɤɚɤ ɩɨɬɟɧɰɢɚɥɶɧɵɣ ɦɚɪɤɟɪ ɚɬɟɪɨɫɤɥɟɪɨɡɚ, ɩɨɫɤɨɥɶɤɭ ɟɝɨ ɫɨɞɟɪɠɚɧɢɟ ɫɧɢɠɚɟɬɫɹ ɤɚɤ ɩɨ ɫɪɚɜɧɟɧɢɸ ɫ ɤɨɧɬɪɨɥɟɦ in vitro, ɬɚɤ ɢ ɜ ɩɥɚɡɦɟ ɤɪɨɜɢ in vivo. Ⱦɪɭɝɢɦ ɦɚɪɤɟɪɨɦ ɜ ɪɚɛɨɬɚɯ ɷɬɨɣ ɠɟ ɝɪɭɩɩɵ ɢɫɫɥɟɞɨɜɚɬɟɥɟɣ ɩɪɢɡɧɚɟɬɫɹ ɤɚɬɟɩɫɢɧ D. ɉɪɢɧɰɢɩɢɚɥɶɧɨ ɧɨɜɭɸ ɦɟɬɨɞɢɤɭ ɢɫɫɥɟɞɨɜɚɧɢɹ ɩɪɨɬɟɨɦɧɨɝɨ ɩɪɨɮɢɥɹ ɛɥɹɲɤɢ ɩɪɟɞɥɨɠɢɥɚ ɝɪɭɩɩɚ David Han [11], ɪɚɡɪɚɛɨɬɚɜɲɚɹ ɬ.ɧ. ɩɪɨɰɟɞɭɪɭ ɩɪɹɦɨɣ ɬɤɚɧɟɜɨɣ ɩɪɨɬɟɨɦɢɤɢ (DTP), ɩɨɡɜɨɥɹɸɳɭɸ ɢɞɟɧɬɢɮɢɰɢɪɨɜɚɬɶ ɛɟɥɤɢ ɜ ɦɢɧɢɦɚɥɶɧɵɯ ɤɨɥɢɱɟɫɬɜɚɯ ɬɤɚɧɢ ɫɨɫɭɞɚ. ɋ ɷɬɨɣ ɰɟɥɶɸ ɛɟɥɤɢ ɷɤɫɬɪɚɝɢɪɭɸɬɫɹ ɢɡ ɮɢɤɫɢɪɨɜɚɧɧɵɯ ɮɨɪɦɚɥɶɞɟɝɢɞɨɦ ɢ ɩɨɝɪɭɠɟɧɧɵɯ ɜ ɩɚɪɚɮɢɧ ɨɛɪɚɡɰɨɜ ɬɤɚɧɢ, ɱɬɨ ɨɛɟɫɩɟɱɢɜɚɟɬ ɢɯ ɛɨɥɟɟ ɷɮɮɟɤɬɢɜɧɨɟ ɪɚɡɞɟɥɟɧɢɟ. ɉɨɥɭɱɟɧɧɵɣ ɩɪɨɮɢɥɶ ɛɥɹɲɤɢ ɢɡ ɤɨɪɨɧɚɪɧɨɣ ɚɪɬɟɪɢɢ ɜɤɥɸɱɚɥ ɜ ɫɟɛɹ 806 ɛɟɥɤɨɜ, ɪɹɞ ɢɡ ɤɨɬɨɪɵɯ ɢ ɪɚɧɟɟ ɫɜɹɡɵɜɚɥɢ ɫ ɪɚɡɜɢɬɢɟɦ ɚɬɟɪɨɫɤɥɟɪɨɡɚ. Ɉɞɧɚɤɨ, ɧɚɪɹɞɭ ɫ ɧɢɦɢ, ɛɵɥɢ ɨɛɧɚɪɭɠɟɧɵ ɜɵɩɨɥɧɹɸɳɢɟ ɪɟɝɭɥɹɬɨɪɧɵɟ ɮɭɧɤɰɢɢ PEDF (pigment-epithelium derived factor), ɩɟɪɢɨɫɬɢɧ (periostin), MFG-E8 (milk fat globule-EGF-factor 8) ɢ aɧɧɟɤɫɢɧ I, ɚ ɬɚɤ107 ɠɟ ɧɟɤɨɬɨɪɵɟ ɮɚɤɬɨɪɵ ɪɨɫɬɚ ɢ ɰɢɬɨɤɢɧɵ. Ⱥɜɬɨɪɵ ɩɨɥɚɝɚɸɬ, ɱɬɨ ɢɦɢ ɜ ɨɫɧɨɜɧɨɦ ɢɞɟɧɬɢɮɢɰɢɪɨɜɚɧɵ ɛɟɥɤɢ ɜɧɟɤɥɟɬɨɱɧɨɝɨ ɦɚɬɪɢɤɫɚ, ɜɨɜɥɟɱɟɧɧɵɟ ɜ ɪɚɡɜɢɬɢɟ ɚɬɟɪɨɫɤɥɟɪɨɡɚ ɢ ɫɩɨɫɨɛɧɵɟ ɦɢɝɪɢɪɨɜɚɬɶ ɢɡ ɦɟɞɢɢ ɜ ɢɧɬɢɦɭ. Ʉɚɤ ɜ ɧɚɲɟɣ ɪɚɛɨɬɟ (ɚɤɰɟɧɬ ɧɚ ɢɫɫɥɟɞɨɜɚɧɢɢ ɬɚɤɢɯ ɫɬɪɭɤɬɭɪ, ɤɚɤ ɢɧɬɢɦɚ ɢ ɦɟɞɢɹ), ɜɧɢɦɚɧɢɟ ɢɫɫɥɟɞɨɜɚɬɟɥɟɣ ɩɪɢɜɥɟɤɚɸɬ ɝɥɚɞɤɨɦɵɲɟɱɧɵɟ ɤɥɟɬɤɢ ɫɨɫɭɞɨɜ (ȽɆɄ), ɱɶɹ ɩɪɨɥɢɮɟɪɚɰɢɹ ɢ ɦɢɝɪɚɰɢɹ ɜɚɠɧɵ ɞɥɹ ɪɚɡɜɢɬɢɹ ɩɚɬɨɥɨɝɢɢ. Ⱦɢɮɮɟɪɟɧɰɢɚɥɶɧɚɹ ɩɪɨɬɟɨɦɢɤɚ ɜɵɹɜɢɥɚ ɜɚɠɧɭɸ ɪɨɥɶ ɯɚɩɟɪɨɧɨɜ, ɚ ɬɚɤɠɟ ɛɟɥɤɨɜ ɰɢɬɨɫɤɟɥɟɬɚ (ɜɢɦɟɧɬɢɧɚ ɢ ɚɤɬɢɧɚ) ɜ ɮɨɪɦɢɪɨɜɚɧɢɢ ɛɥɹɲɤɢ, ɩɪɨɞɨɥɠɚɟɬɫɹ ɢɡɭɱɟɧɢɟ ɜɥɢɹɧɢɹ ɧɚ ȽɆɄ ɨɤɢɫɥɟɧɧɵɯ Ʌɉɇɉ, ɨɤɢɫɥɢɬɟɥɶɧɨɝɨ ɫɬɪɟɫɫɚ, ɦɟɯɚɧɢɱɟɫɤɨɝɨ ɝɟɧɨɞɢɧɚɦɢɱɟɫɤɨɝɨ ɧɚɩɪɹɠɟɧɢɹ. ȼ ɱɚɫɬɧɨɫɬɢ, ɜ ɩɨɫɥɟɞɧɟɦ ɫɥɭɱɚɟ ɨɛɧɚɪɭɠɟɧɨ ɢɡɦɟɧɟɧɢɟ ɭɪɨɜɧɟɣ ɝɟɥɫɨɥɢɧɚ, hsp27 ɢ ɋɚɪZ [64]. Ɂɞɟɫɶ ɭɦɟɫɬɧɨ ɨɬɦɟɬɢɬɶ, ɱɬɨ ɢ ɞɪɭɝɢɟ ɚɜɬɨɪɵ ɨɛɧɚɪɭɠɢɥɢ ɭɜɟɥɢɱɟɧɢɟ ɷɤɫɩɪɟɫɫɢɢ hsp60 ɢ hsp70 ɩɪɢ ɚɬɟɪɨɫɤɥɟɪɨɬɢɱɟɫɤɨɦ ɩɨɪɚɠɟɧɢɢ [98]. ɋ ɭɱɟɬɨɦ ɩɪɟɞɫɬɚɜɥɟɧɧɵɯ ɡɞɟɫɶ ɪɟɡɭɥɶɬɚɬɨɜ ɢɫɫɥɟɞɨɜɚɧɢɣ, ɫɯɨɞɧɵɯ ɫ ɜɵɩɨɥɧɟɧɧɵɦɢ ɧɚɦɢ, ɫɥɟɞɭɟɬ ɭɤɚɡɚɬɶ, ɤɚɤ ɦɢɧɢɦɭɦ, ɧɚ ɩɨɞɬɜɟɪɠɞɟɧɢɟ ɪɨɥɢ ɜ ɮɨɪɦɢɪɨɜɚɧɢɢ ɚɬɟɪɨɫɤɥɟɪɨɬɢɱɟɫɤɨɣ ɛɥɹɲɤɢ ɬɚɤɢɯ ɧɢɡɤɨɦɨɥɟɤɭɥɹɪɧɵɯ ɛɟɥɤɨɜ, ɤɚɤ ɚɧɧɟɤɫɢɧɵ ɢ ɛɟɥɤɢ ɬɟɩɥɨɜɨɝɨ ɲɨɤɚ. ɉɪɢ ɷɬɨɦ ɭɦɟɫɬɧɨ ɫɧɨɜɚ ɭɤɚɡɚɬɶ ɧɚ ɪɚɛɨɬɭ Tao ɫ ɫɨɬɪɭɞɧɢɤɚɦɢ [86], ɤɨɬɨɪɵɣ ɨɛɧɚɪɭɠɢɥ, ɱɬɨ ɛɟɥɤɢ ɬɟɩɥɨɜɨɝɨ ɲɨɤɚ (ɢ ɯɚɩɟɪɨɧɵ) ɞɨɦɢɧɢɪɭɸɬ ɜ CD34+ ɤɥɟɬɤɚɯ. Ɍɟɦ ɧɟ ɦɟɧɟɟ, ɫɨɜɟɪɲɟɧɧɨ ɹɫɧɨ, ɱɬɨ ɞɥɹ ɭɬɨɱɧɟɧɢɹ ɪɨɥɢ ɛɟɥɤɨɜ ɜ ɚɬɟɪɨɝɟɧɟɡɟ ɫ ɩɨɦɨɳɶɸ ɩɪɨɬɟɨɦɢɤɢ ɧɟɨɛɯɨɞɢɦɵ ɞɚɥɶɧɟɣɲɢɟ ɢɫɫɥɟɞɨɜɚɧɢɹ ɧɚ ɜɵɪɟɡɚɟɦɵɯ ɥɚɡɟɪɨɦ ɦɢɤɪɨɭɱɚɫɬɤɚɯ ɫɨɫɭɞɨɜ, ɚ ɬɚɤɠɟ ɨɰɟɧɤɚ ɩɨɫɬɬɪɚɧɫɥɹɰɢɨɧɧɵɯ ɦɨɞɢɮɢɤɚɰɢɣ ɛɟɥɤɨɜ, ɜ ɱɚɫɬɧɨɫɬɢ, ɨɤɢɫɥɢɬɟɥɶɧɨɝɨ ɯɚɪɚɤɬɟɪɚ, ɱɬɨ ɦɨɠɟɬ ɛɵɬɶ ɩɨɥɟɡɧɵɦ ɤɚɤ ɞɥɹ ɨɛɧɚɪɭɠɟɧɢɹ ɧɨɜɵɯ ɦɚɪɤɟɪɨɜ ɩɚɬɨɥɨɝɢɢ, ɬɚɤ ɢ ɞɥɹ ɰɟɥɟɣ ɬɟɪɚɩɢɢ. 108 ȼ ɬɨ ɠɟ ɜɪɟɦɹ ɩɨɤɚ ɜɟɫɶɦɚ ɫɨɦɧɢɬɟɥɶɧɨ, ɱɬɨ ɩɪɨɮɢɥɚɤɬɢɤɚ ɢ ɥɟɱɟɧɢɟ ɚɬɟɪɨɫɤɥɟɪɨɡɚ ɫ ɩɨɦɨɳɶɸ ȽɋɄ – ɞɨɫɬɚɬɨɱɧɨ ɛɥɢɡɤɚɹ ɩɟɪɫɩɟɤɬɢɜɚ. ɋ ɨɞɧɨɣ ɫɬɨɪɨɧɵ, ɟɳɟ ɜ 2001 ɝ. ɛɵɥɨ ɩɪɨɞɟɦɨɧɫɬɪɢɪɨɜɚɧɨ, ɱɬɨ ɜɧɭɬɪɢɜɟɧɧɨɟ ɜɜɟɞɟɧɢɟ CD34+ ɤɥɟɬɨɤ ɜɟɞɟɬ ɤ ɭɥɭɱɲɟɧɢɸ ɮɭɧɤɰɢɨɧɢɪɨɜɚɧɢɹ ɋɋɋ [50]. ɋ ɞɪɭɝɨɣ ɫɬɨɪɨɧɵ, ɦɟɯɚɧɢɡɦɵ, ɩɨɫɪɟɞɫɬɜɨɦ ɤɨɬɨɪɵɯ ɬɪɚɧɫɩɥɚɧɬɢɪɨɜɚɧɧɵɟ ɋɄ ɜɥɢɹɸɬ ɧɚ ɫɨɫɭɞɵ, ɨɫɬɚɸɫɹ ɦɚɥɨɩɨɧɹɬɧɵɦɢ. ȼɨɡɦɨɠɧɨ, ɋɄ ɞɢɮɮɟɪɟɧɰɢɪɭɸɬɫɹ ɜ ɤɥɟɬɤɢ, ɫɩɨɫɨɛɧɵɟ ɤ ɡɚɦɟɳɟɧɢɸ ɫɬɪɭɤɬɭɪ, ɩɨɪɚɠɟɧɧɵɯ ɜ ɩɪɨɰɟɫɫɟ ɚɬɟɪɨɝɟɧɟɡɚ (ɧɟɨɚɧɝɢɨɝɟɧɟɡ). ȼɦɟɫɬɨ ɩɪɹɦɵɯ ɞɨɤɚɡɚɬɟɥɶɫɬɜ ɬɚɤɨɣ ɜɨɡɦɨɠɧɨɫɬɢ ɫɭɳɟɫɬɜɭɸɬ ɩɪɟɞɩɨɥɨɠɟɧɢɹ ɨ ɦɟɯɚɧɢɡɦɚɯ ɢ ɮɚɤɬɨɪɚɯ, ɦɨɞɭɥɢɪɭɸɳɢɯ ɤɥɟɬɨɱɧɨɟ ɞɟɥɟɧɢɟ, ɚɩɨɩɬɨɡ, ɝɨɦɟɨɫɬɚɡ ɢ ɬ.ɩ. ɉɪɢ ɷɬɨɦ ɛɨɥɟɟ ɢɡɭɱɟɧɧɵɦɢ ɹɜɥɹɸɬɫɹ ɷɦɛɪɢɨɧɚɥɶɧɵɟ ɋɄ, ɬɨɝɞɚ ɤɚɤ ɜɨɡɦɨɠɧɨɫɬɢ ȽɋɄ ɢɡɜɟɫɬɧɵ ɝɨɪɚɡɧɨ ɦɟɧɶɲɟ. ȼ ɧɚɲɟɣ ɪɚɛɨɬɟ ɧɚɪɹɞɭ ɫ ȽɋɄ ɩɪɨɬɟɨɦɧɵɦ ɢɫɫɥɟɞɨɜɚɧɢɹɦ ɛɵɥɢ ɩɨɞɜɟɪɝɧɭɬɵ ɨɫɬɟɨɛɥɚɫɬɵ ɢ ȽɆɄ ɚɪɬɟɪɢɣ. ɉɨɞɱɟɪɤɧɟɦ ɟɳɟ ɪɚɡ, ɱɬɨ ɥɨɤɚɥɶɧɨɟ ɦɢɤɪɨɨɤɪɭɠɟɧɢɟ, ɜ ɤɨɬɨɪɨɟ ɜɯɨɞɹɬ ɨɫɬɟɨɛɥɚɫɬɵ ɢ ȽɆɄ, ɨɩɪɟɞɟɥɹɟɬ ɤɚɤ ɧɚɩɪɚɜɥɟɧɢɟ ɞɢɮɮɟɪɟɧɰɢɚɰɢɢ ȽɋɄ, ɬɚɤ ɢ ɮɢɛɪɨɡ ɢɧɬɢɦɵ ɫɬɟɧɤɢ ɫɨɫɭɞɨɜ, ɯɨɧɞɪɨ- ɢ ɨɫɬɟɨɝɟɧɟɡ ɫ ɩɨɫɥɟɞɭɸɳɟɣ ɤɚɥɶɰɢɮɢɤɚɰɢɟɣ. Ɍɚɤɢɦ ɨɛɪɚɡɨɦ, ɜɫɟ ɷɬɢ ɬɪɢ ɫɬɪɭɤɬɭɪɧɵɯ ɷɥɟɦɟɧɬɚ – ɜɡɚɢɦɨɡɚɜɢɫɢɦɵ. Ⱥɬɟɪɨɫɤɥɟɪɨɬɢɱɟɫɤɢɟ ɩɨɪɚɠɟɧɢɹ ɫɨɞɟɪɠɚɬ ɨɫɬɟɨɛɥɚɫɬ-ɩɨɞɨɛɧɵɟ ɤɥɟɬɤɢ, ɭɥɶɬɪɚɫɬɪɭɤɬɭɪɚ ɤɨɬɨɪɵɯ ɧɚɩɨɦɢɧɚɟɬ ȽɆɄ. ȼ ɬɨ ɠɟ ɜɪɟɦɹ ɩɪɟɞɩɨɥɚɝɚɟɬɫɹ, ɱɬɨ ɨɫɬɟɨɛɥɚɫɬɵ ɩɪɨɢɫɯɨɞɹɬ ɢɡ ɋɄ, ɩɪɨɧɢɤɚɸɳɢɯ ɜ ɚɬɟɪɨɫɤɥɟɪɨɬɢɱɟɫɤɢɟ ɛɥɹɲɤɢ ɢɡ ɤɪɨɜɹɧɨɝɨ ɪɭɫɥɚ. ȼɢɞɢɦɨ, ɫɥɟɞɭɸɳɢɣ ɲɚɝ ɞɥɹ ɩɨɧɢɦɚɧɢɹ ɩɪɨɰɟɫɫɨɜ ɚɬɟɪɨɝɟɧɟɡɚ ɢ ɜɨɡɦɨɠɧɨɫɬɟɣ ȽɋɄ ɞɥɹ ɟɝɨ ɬɟɪɚɩɢɢ – ɨɞɧɨɜɪɟɦɟɧɧɨɟ ɧɚɛɥɸɞɟɧɢɟ ɫ ɩɨɦɨɳɶɸ ɩɪɨɬɟɨɦɢɤɢ ɡɚ ɞɢɧɚɦɢɤɨɣ ɢɡɦɟɧɟɧɢɹ ɋɄ, ȽɆɄ ɢ ɨɫɬɟɨɛɥɚɫɬɨɜ ɩɪɢ ɪɚɡɜɢɬɢɢ ɷɬɨɣ ɩɚɬɨɥɨɝɢɢ. 109 110 ȼɕȼɈȾɕ 1. Ɉɩɬɢɦɢɡɢɪɨɜɚɧ ɚɥɝɨɪɢɬɦ ɩɪɨɬɟɨɦɧɨɝɨ ɚɧɚɥɢɡɚ – ɫɨɡɞɚɧɚ ɟɞɢɧɚɹ ɫɯɟɦɚ ɢɫɫɥɟɞɨɜɚɧɢɹ ɛɟɥɤɨɜɵɯ ɩɪɨɮɢɥɟɣ, ɭɩɪɨɳɚɸɳɚɹ ɫɪɚɜɧɟɧɢɟ ɞɚɧɧɵɯ, ɩɨɥɭɱɟɧɧɵɯ ɧɚ ɬɚɤɢɯ ɪɚɡɧɵɯ ɨɛɴɟɤɬɚɯ, ɤɚɤ ɨɫɬɟɨɛɥɚɫɬɵ, ɦɨɧɨɧɭɤɥɟɚɪɧɵɟ ɤɥɟɬɤɢ, CD34+ȽɋɄ ɢ ɢɧɬɢɦɨ-ɦɟɞɢɚɥɶɧɵɣ ɫɥɨɣ ɚɨɪɬɵ ɱɟɥɨɜɟɤɚ. ɍɫɨɜɟɪɲɟɧɫɬɜɨɜɚɧɧɵɣ ɦɟɬɨɞ – ɤɨɦɛɢɧɚɰɢɹ 2D-ɷɥɟɤɬɪɨɮɨɪɟɡɚ ɫ ɮɪɚɤɰɢɨɧɢɪɨɜɚɧɢɟɦ ɤɥɟɬɨɱɧɵɯ ɨɪɝɚɧɟɥɥ ɩɨɡɜɨɥɹɟɬ ɧɟ ɬɨɥɶɤɨ ɩɪɨɜɟɫɬɢ ɩɪɨɬɟɨɦɧɵɣ ɚɧɚɥɢɡ ɤɥɟɬɨɤ, ɧɨ ɢ ɩɨɥɭɱɢɬɶ ɢɧɮɨɪɦɚɰɢɸ ɨ ɜɧɭɬɪɢɤɥɟɬɨɱɧɨɣ ɥɨɤɚɥɢɡɚɰɢɢ ɫɩɟɰɢɮɢɱɟɫɤɢɯ ɛɟɥɤɨɜ. 2. ɂɡɭɱɟɧɨ ɫ ɩɨɦɨɳɶɸ ɩɪɨɬɟɨɦɢɤɢ ɩɨɜɟɞɟɧɢɟ ɛɟɥɤɨɜ ɨɫɬɟɨ- ɛɥɚɫɬɨɜ, ɢɡɦɟɧɹɸɳɢɯɫɹ ɩɨɞ ɞɟɣɫɬɜɢɟɦ ɩɚɪɚɬɢɪɟɨɢɞɧɨɝɨ ɝɨɪɦɨɧɚ, ɹɜɥɹɸɳɟɝɨɫɹ ɜɚɠɧɵɦ ɤɨɦɩɨɧɟɧɬɨɦ ɧɢɲɢ ȽɋɄ. ɉɨɤɚɡɚɧɨ, ɱɬɨ ɩɪɨɬɟɨɦɧɵɣ ɚɧɚɥɢɡ ɦɨɠɟɬ ɩɪɢɦɟɧɹɬɶɫɹ ɞɥɹ ɧɚɛɥɸɞɟɧɢɹ ɡɚ ɞɢɧɚɦɢɤɨɣ ɢɡɦɟɧɟɧɢɹ ɛɟɥɤɨɜ ɜ ɨɬɜɟɬ ɧɚ ɜɧɟɲɧɢɟ ɜɨɡɞɟɣɫɬɜɢɹ, ɱɬɨ, ɜ ɫɜɨɸ ɨɱɟɪɟɞɶ, ɞɚɫɬ ɜɨɡɦɨɠɧɨɫɬɶ ɩɪɨɜɨɞɢɬɶ ɷɤɫɩɚɧɫɢɸ ȽɋɄ ɜ ɭɫɥɨɜɢɹɯ in vitro. 3. Ɉɩɢɫɚɧ ɩɪɨɬɟɨɦɧɵɣ ɩɪɨɮɢɥɶ ɆɇɄ ɢ CD34+ȽɋɄ ɫ ɜɵɫɨɤɢɦ ɪɚɡɪɟɲɟɧɢɟɦ, ɬɨ ɟɫɬɶ ɫɞɟɥɚɧ ɜɚɠɧɵɣ ɲɚɝ ɜ ɩɨɫɬɪɨɟɧɢɢ ɝɥɨɛɚɥɶɧɨɝɨ ɩɪɨɬɟɨɦɧɨɝɨ ɩɪɨɮɢɥɹ ɦɨɧɨɧɭɤɥɟɚɪɧɵɯ ɤɥɟɬɨɤ ɢ CD34+ ȽɋɄ. ɉɪɨɜɟɞɟɧɚ ɢɞɟɧɬɢɮɢɤɚɰɢɹ ɛɟɥɤɨɜ, ɩɪɢɫɭɬɫɬɜɭɸɳɢɯ ɜ CD34+ȽɋɄ. 4. ɋɨɩɨɫɬɚɜɥɟɧɵ ɩɪɨɬɟɨɦɧɵɟ ɩɪɨɮɢɥɢ ɢɧɬɢɦɵ ɢ ɦɟɞɢɢ ɫɨɫɭ- ɞɨɜ ɜ ɩɪɨɰɟɫɫɟ ɚɬɟɪɨɝɟɧɟɡɚ. ȼɵɹɜɥɟɧɵ ɛɟɥɤɢ, ɭɪɨɜɧɢ ɤɨɬɨɪɵɯ ɢɡɦɟɧɹɸɬɫɹ ɩɪɢ ɪɚɡɜɢɬɢɢ ɚɬɟɪɨɫɤɥɟɪɨɬɢɱɟɫɤɨɝɨ ɩɨɪɚɠɟɧɢɹ ɜ ɢɧɬɢɦɨɦɟɞɢɚɥɶɧɨɦ ɫɥɨɟ ɚɨɪɬɵ ɱɟɥɨɜɟɤɚ. ɉɨɞɬɜɟɪɠɞɟɧɚ ɪɨɥɶ ɜ ɮɨɪɦɢɪɨɜɚɧɢɢ ɚɬɟɪɨɫɤɥɟɪɨɬɢɱɟɫɤɨɣ ɛɥɹɲɤɢ ɬɚɤɢɯ ɧɢɡɤɨɦɨɥɟɤɭɥɹɪɧɵɯ ɛɟɥɤɨɜ, ɤɚɤ ɚɧɧɟɤɫɢɧɵ ɢ ɛɟɥɤɢ ɬɟɩɥɨɜɨɝɨ ɲɨɤɚ. 111 5. ɉɨɥɭɱɟɧɧɵɟ ɞɚɧɧɵɟ ɩɨɞɬɜɟɪɠɞɚɸɬ ɬɚɤɠɟ ɩɨɬɟɧɰɢɚɥɶɧɭɸ ɜɨɡɦɨɠɧɨɫɬɶ ɢɫɩɨɥɶɡɨɜɚɧɢɹ ȽɋɄ ɜ ɬɟɪɚɩɢɢ ɚɬɟɪɨɫɤɥɟɪɨɡɚ ɢ ɭɤɚɡɵɜɚɸɬ ɧɚ ɩɟɪɫɩɟɤɬɢɜɧɵɟ ɧɚɩɪɚɜɥɟɧɢɹ ɩɪɨɬɟɨɦɧɵɯ ɢɫɫɥɟɞɨɜɚɧɢɣ ɬɚɤɢɯ ɨɛɴɟɤɬɨɜ, ɤɚɤ ɫɬɜɨɥɨɜɵɟ ɤɥɟɬɤɢ, ɨɫɬɟɨɛɥɚɫɬɵ ɢ ɝɥɚɞɤɨɦɵɲɟɱɧɵɟ ɤɥɟɬɤɢ ɤɪɨɜɟɧɨɫɧɵɯ ɫɨɫɭɞɨɜ. 112 5. ɋɉɂɋɈɄ ɅɂɌȿɊȺɌɍɊɕ 1. Ƚɚɣɤɨɜɚɹ Ʌ.Ȼ., Ʉɭɯɚɪɱɢɤ Ƚ.Ⱥ., ɇɟɫɬɟɪɨɜɚ ɇ.ɇ., ȼɚɜɢɥɨɜɚ Ɍ.ȼ., Ȼɭɪɛɟɥɥɨ Ⱥ.Ɍ., ɒɚɛɪɨɜ Ⱥ.ȼ. ɋɨɜɪɟɦɟɧɧɵɟ ɥɚɛɨɪɚɬɨɪɧɵɟ ɦɚɪɤɟɪɵ ɜ ɨɩɪɟɞɟɥɟɧɢɢ ɩɪɨɝɧɨɡɚ ɩɪɢ ɨɫɬɪɨɦ ɤɨɪɨɧɚɪɧɨɦ ɫɢɧɞɪɨɦɟ ɢ ɦɨɧɢɬɨɪɢɧɝɟ ɬɟɪɚɩɢɢ // ȼɟɫɬɧɢɤ ɚɪɢɬɦɨɥɨɝɢɢ. – ʋ 58. – 2009. – ɋ. 52-59. 2. ɉɟɬɪɨɜɚ Ɍ.ȼ., ɋɜɢɧɚɪɟɜɚ Ⱦ.Ⱥ., ɇɢɮɨɧɬɨɜɚ ɂ.ɇ. ɢ ɞɪ. ɋɬɪɨ- ɦɚɥɶɧɚɹ ɪɟɝɭɥɹɰɢɹ ɫɬɜɨɥɨɜɵɯ ɤɪɨɜɟɬɜɨɪɧɵɯ ɤɥɟɬɨɤ ɜ ɞɥɢɬɟɥɶɧɵɯ ɤɭɥɶɬɭɪɚɯ ɤɨɫɬɧɨɝɨ ɦɨɡɝɚ ɱɟɥɨɜɟɤɚ ɩɨɞ ɞɟɣɫɬɜɢɟɦ ɩɚɪɚɬɢɪɟɨɢɞɧɨɝɨ ɝɨɪɦɨɧɚ // Ʉɥɟɬɨɱɧɵɟ ɬɟɯɧɨɥɨɝɢɢ ɜ ɛɢɨɥɨɝɢɢ ɢ ɦɟɞɢɰɢɧɟ. – 2006. - ʋ 4. – ɋ. 218-222. 3. Ɋɚɝɢɧɨ ɘ.ɂ., Ȼɚɭɦ ȼ.Ⱥ., ɉɨɥɨɧɫɤɚɹ ə.ȼ ɢ ɞɪ. Ⱥɬɟɪɨɫɤɥɟɪɨɡ ɢ ɨɤɢɫɥɢɬɟɥɶɧɵɟ ɩɪɨɰɟɫɫɵ. ɇɨɜɵɟ ɫɩɨɫɨɛɵ ɨɰɟɧɤɢ ɨɤɢɫɥɢɬɟɥɶɧɨɣ ɦɨɞɢɮɢɤɚɰɢɢ ɛɟɥɤɨɜ // Ȼɸɥɥɟɬɟɧɶ ɋɈ ɊȺɆɇ. – 2006. – ʋ 4(122). – ɋ. 67-73. 4. ɋɜɢɧɚɪɟɜɚ Ⱦ.Ⱥ., ɇɢɮɨɧɬɨɜɚ ɂ.ɇ., ɑɟɪɬɤɨɜ ɂ.Ʌ., Ⱦɪɢɡɫ ɇ.ɂ. ɂɡɦɟɧɟɧɢɟ ɯɨɭɦɢɧɝɚ ɤɪɨɜɟɬɜɨɪɧɵɯ ɤɥɟɬɨɤ-ɩɪɟɞɲɟɫɬɜɟɧɧɢɤɨɜ ɩɨɫɥɟ ɞɥɢɬɟɥɶɧɨɝɨ ɜɨɡɞɟɣɫɬɜɢɹ ɩɚɪɚɬɢɪɟɨɢɞɧɨɝɨ ɝɨɪɦɨɧɚ // Ȼɸɥɥ ɷɤɫɩɟɪ ɛɢɨɥ ɦɟɞ. - 2006. – T. 142. – C. 97-101. 5. ɋɨɛɨɥɟɜɚ ɗ.Ʌ., ɉɨɩɤɨɜɚ ȼ.Ɇ. 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Methods. – 2007. – Vol. 319. – Ɋ. 1–5. 125 126 ɋɉɂɋɈɄ ɋɈɄɊȺɓȿɇɂɃ ȽɋɄ – ɝɟɦɨɩɨɷɬɢɱɟɫɤɢɟ ɫɬɜɨɥɨɜɵɟ ɤɥɟɬɤɢ Ⱦɗ – ɞɜɭɦɟɪɧɵɟ ɷɥɟɤɬɪɨɮɨɪɟɝɪɚɦɦɵ ɂɎȻ – ɢɡɨɬɨɧɢɱɟɫɤɢɣ ɮɨɫɮɚɬɧɵɣ ɛɭɮɟɪ, ɪɇ 7,4 ɂɗɎ – ɢɡɨɷɥɟɤɬɪɢɱɟɫɤɨɟ ɮɨɤɭɫɢɪɨɜɚɧɢɟ Ʌɉɇɉ – ɥɢɩɨɩɪɨɬɟɢɞɵ ɧɢɡɤɨɣ ɩɥɨɬɧɨɫɬɢ ɆɇɄ – ɦɨɧɨɧɭɤɥɟɚɪɧɵɟ ɤɥɟɬɤɢ MCK – ɦɟɡɟɧɯɢɦɚɥɶɧɵɟ ɫɬɜɨɥɨɜɵɟ ɤɥɟɬɤɢ ɉɄ – ɩɭɩɨɜɢɧɧɚɹ ɤɪɨɜɶ ɉɌȽ – ɩɚɪɚɬɢɪɟɨɢɞɧɵɣ ɝɨɪɦɨɧ ɋɄ – ɫɬɜɨɥɨɜɵɟ ɤɥɟɬɤɢ ɋɋɋ – ɫɟɪɞɟɱɧɨɫɨɫɭɞɢɫɬɚɹ ɫɢɫɬɟɦɚ Ɍɏɍ – ɬɪɢɯɥɨɪɭɤɫɭɫɧɚɹ ɤɢɫɥɨɬɚ ɎȻɋ – ɮɟɬɚɥɶɧɚɹ ɛɵɱɶɹ ɫɵɜɨɪɨɬɤɚ ɗȾɌȺ – ɷɬɢɥɟɧɞɢɚɦɢɧɬɟɬɪɚɭɤɫɭɫɧɚɹ ɤɢɫɥɨɬɚ CD34+ ȽɋɄ – ɝɟɦɨɩɨɷɬɢɱɟɫɤɢɟ ɫɬɜɨɥɨɜɵɟ ɤɥɟɬɤɢ, ɧɟɫɭɳɢɟ ɚɧɬɢɝɟɧ CD34 2D – ɦɟɬɨɞ ɞɜɭɦɟɪɧɨɝɨ ɝɟɥɶ-ɷɥɟɤɬɪɨɮɨɪɟɡɚ ɧɚ ɩɨɥɢɚɤɪɢɥɚɦɢɞɟ FACS – aɤɬɢɜɢɪɨɜɚɧɧɚɹ ɮɥɭɨɪɟɫɰɟɧɰɢɟɣ ɫɨɪɬɢɪɨɜɤɚ ɤɥɟɬɨɤ GFP – ɡɟɥɟɧɵɣ ɮɥɭɨɪɟɫɰɢɪɭɸɳɢɣ ɛɟɥɨɤ HSP – ɛɟɥɤɢ ɬɟɩɥɨɜɨɝɨ ɲɨɤɚ (heat-shock proteins ) IMDM – ɪɨɫɬɨɜɚɹ ɫɪɟɞɚ ɞɥɹ ɤɭɥɶɬɢɜɢɪɨɜɚɧɢɹ ɤɥɟɬɨɤ Dulbecco M IPG ɫɬɪɢɩɵ – ɝɟɥɟɜɵɟ ɩɨɥɨɫɤɢ ɢɦɦɨɛɢɥɢɡɨɜɚɧɧɵɯ ɝɪɚɞɢɟɧɬɨɜ pH IL – ɢɧɬɟɪɥɟɣɤɢɧ Jagged1 (Jag1) – ɫɢɧɬɟɬɢɱɟɫɤɢɣ (ɦɵɲɢɧɵɣ) ɪɟɤɨɦɛɢɧɚɧɬɧɵɣ ɩɟɩɬɢɞ, ɥɢɝɚɧɞ 127 MALDI–TOF (matrix assisted laser deionization time of flight) – ɦɚɬɪɢɱɧɚɹ ɥɚɡɟɪɧɚɹ ɞɟɫɨɪɛɰɢɨɧɧɚɹ ɢɨɧɢɡɚɰɢɨɧɚɹ ɜɪɟɦɹɩɪɨɥɟɬɧɚɹ ɦɚɫɫ-ɫɩɟɤɬɪɨɦɟɬɪɢɹ Notch-1 – ɪɟɰɟɩɬɨɪ, ɩɪɢɫɭɬɫɬɜɭɸɳɢɣ ɧɚ ɩɨɜɟɪɯɧɨɫɬɢ ɤɥɟɬɨɤ SCF – ɮɚɤɬɨɪ ɫɬɜɨɥɨɜɵɯ ɤɥɟɬɨɤ TGF – ɬɪɚɧɫɮɨɪɦɢɪɭɸɳɢɣ ɮɚɤɬɨɪ ɪɨɫɬɚ TPO – ɬɪɨɦɛɨɩɪɨɬɟɢɧ. 128 ɉɊɂɅɈɀȿɇɂȿ Ȼɟɥɤɢ, ɢɞɟɧɬɢɮɢɰɢɪɨɜɚɧɧɵɟ ɦɟɬɨɞɚɦɢ ɩɪɨɬɟɨɦɢɤɢ ɜ ɬɪɟɯ ɮɪɚɤɰɢɹɯ, ɜɵɞɟɥɟɧɧɵɯ ɢɡ CD34+ȽɋɄ Ɍɚɛɥɢɰɚ 1 ȼɟɪɨɹɬɧɨɫɬɶ ɇɨɦɟɪ ʋ ɩ/ɩ ɫɨɜɩɚɞɟɧɢɹ ɩɹɬɧɚ ID ɛɟɥɤɨɜ ɞɥɹ CD34+ȽɋɄ (1-ɹ ɮɪɚɤɰɢɹ, 1-ɹ ɩɨɜɬɨɪɧɨɫɬɶ) (%) 1 2 3 4 1 93.53 Immunoglobulin superfamily member 8 precursor CD81 partner 3 521 Glu Trp Ile EWI motif containing protein 2 EWI 2 Keratinocytes associated transmembrane protein 4 KCT 4 LIR D1 CD316 antigen Homo sapiens Human 2 92.45 Hemoglobin subunit alpha Hemoglobin alpha chain Alpha globin 943 Homo sapiens Human 3 85.65 Hemoglobin subunit alpha Hemoglobin alpha chain Alpha globin 963 Homo sapiens Human 4 83.52 Immunoglobulin superfamily member 8 precursor CD81 partner 3 498 Glu Trp Ile EWI motif containing protein 2 EWI 2 Keratinocytes associated transmembrane protein 4 KCT 4 LIR D1 CD316 antigen Homo sapiens Human 5 76.42 Hemoglobin subunit gamma 2 Hemoglobin gamma 2 chain Gamma 971 2 globin Hemoglobin gamma G chain Hb F Ggamma Homo sapiens Human 6 68.30 Cystinosin Homo sapiens Human 773 7 68.18 Hemoglobin subunit gamma 1 Hemoglobin gamma 1 chain Gamma 786 1 globin Hemoglobin gamma A chain Hb F Agamma Homo sapiens Human 8 58.09 Zinc finger protein 250 Zinc finger protein 647 Homo sapiens Hu583 man 9 56.07 Hemoglobin subunit gamma 2 Hemoglobin gamma 2 chain Gamma 806 2 globin Hemoglobin gamma G chain Hb F Ggamma Homo sapiens Human 10 53.12 Vacuolar protein sorting associated protein 25 hVps25 ELL asso672 ciated protein of 20 kDa Dermal papilla derived protein 9 Homo sapiens Human 11 48.43 Zinc finger protein 250 Zinc finger protein 647 Homo sapiens Human 740 12 47.13 Zinc finger protein 250 Zinc finger protein 647 Homo sapiens Hu385 man 13 47.13 Zinc finger protein 250 Zinc finger protein 647 Homo sapiens Hu385 man 14 46.11 Zinc finger protein 250 Zinc finger protein 647 Homo sapiens Hu453 man 15 46.05 Immunoglobulin superfamily member 8 precursor CD81 partner 3 550 Glu Trp Ile EWI motif containing protein 2 EWI 2 Keratinocytes associated transmembrane protein 4 KCT 4 LIR D1 CD316 antigen Homo sapiens Human 129 1 16 2 45.42 17 18 19 44.29 39.44 37.86 20 37.73 21 36.82 22 36.20 23 24 25 35.21 34.70 33.75 26 33.08 27 28.49 28 28.19 29 27.88 30 27.76 31 26.56 32 25.73 33 24.53 34 24.18 35 23.66 36 23.54 3 Immunoglobulin superfamily member 8 precursor CD81 partner 3 Glu Trp Ile EWI motif containing protein 2 EWI 2 Keratinocytes associated transmembrane protein 4 KCT 4 LIR D1 CD316 antigen Homo sapiens Human Chloride channel protein 3 ClC 3 Homo sapiens Human Bcl-2-modifying factor Homo sapiens Human Immunoglobulin superfamily member 8 precursor CD81 partner 3 Glu Trp Ile EWI motif containing protein 2 EWI 2 Keratinocytes associated transmembrane protein 4 KCT 4 LIR D1 CD316 antigen Homo sapiens Human Epididymal-specific lipocalin 9 precursor MUP like lipocalin Homo sapiens Human Low-density lipoprotein receptor related protein 8 precursor Apolipoprotein E receptor 2 Homo sapiens Human Hemoglobin subunit gamma 1 Hemoglobin gamma 1 chain Gamma 1 globin Hemoglobin gamma A chain Hb F Agamma Homo sapiens Human Uncharacterized protein KIAA0196 Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human Epididymal-specific lipocalin 9 precursor MUP like lipocalin Homo sapiens Human Vacuolar protein sorting associated protein 25 hVps25 ELL associated protein of 20 kDa Dermal papilla derived protein 9 Homo sapiens Human Selenocysteine-specific elongation factor Elongation factor sec Eukaryotic elongation factor selenocysteine tRNA specific Homo sapiens Human Immunoglobulin superfamily member 8 precursor CD81 partner 3 Glu Trp Ile EWI motif containing protein 2 EWI 2 Keratinocytes associated transmembrane protein 4 KCT 4 LIR D1 CD316 antigen Homo sapiens Human Zinc finger protein 250 Zinc finger protein 647 Homo sapiens Human Immunoglobulin superfamily member 8 precursor CD81 partner 3 Glu Trp Ile EWI motif containing protein 2 EWI 2 Keratinocytes associated transmembrane protein 4 KCT 4 LIR D1 CD316 antigen Homo sapiens Human DNA-directed RNA polymerase mitochondrial precursor EC 2 7 7 6 MtRPOL Homo sapiens Human Zinc finger protein 250 Zinc finger protein 647 Homo sapiens Human Zinc finger protein 250 Zinc finger protein 647 Homo sapiens Human Zinc finger protein 250 Zinc finger protein 647 Homo sapiens Human Hemoglobin subunit gamma 2 Hemoglobin gamma 2 chain Gamma 2 globin Hemoglobin gamma G chain Hb F Ggamma Homo sapiens Human Transcription factor MafK Erythroid transcription factor NF E2 p18 subunit Homo sapiens Human 4 528 597 1017 630 970 901 814 588 883 788 491 593 629 598 640 591 581 736 522 851 611 130 1 37 2 22.94 38 22.57 39 22.53 40 22.37 41 42 43 44 22.34 22.34 22.34 21.74 45 21.28 46 20.71 47 48 49 50 20.70 20.48 20.45 20.10 51 19.29 52 19.04 53 19.03 54 18.76 55 18.75 56 18.75 57 58 59 17.59 17.59 17.37 60 61 62 63 64 17.27 17.27 16.13 15.91 15.87 3 Zinc finger protein 250 Zinc finger protein 647 Homo sapiens Human Zinc finger protein 250 Zinc finger protein 647 Homo sapiens Human Zinc finger protein 250 Zinc finger protein 647 Homo sapiens Human Immunoglobulin superfamily member 8 precursor CD81 partner 3 Glu Trp Ile EWI motif containing protein 2 EWI 2 Keratinocytes associated transmembrane protein 4 KCT 4 LIR D1 CD316 antigen Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human Beta-defensin 118 precursor Defensin beta 118 Beta defensin 18 DEFB 18 Epididymal secretory protein 13 6 ESP13 6 Homo sapiens Human Actin-binding Rho activating protein Striated muscle activator of Rho dependent signaling STARS Homo sapiens Human Beta-defensin 118 precursor Defensin beta 118 Beta defensin 18 DEFB 18 Epididymal secretory protein 13 6 ESP13 6 Homo sapiens Human Uncharacterized protein C9orf79 Homo sapiens Human Uncharacterized protein C9orf79 Homo sapiens Human Glial fibrillary acidic protein astrocyte GFAP Homo sapiens Human Ladinin 1 Lad 1 120 kDa linear IgA bullous dermatosis antigen 97 kDa linear IgA bullous dermatosis antigen Linear IgA disease antigen homolog LadA Homo sapiens Human Epididymal-specific lipocalin 9 precursor MUP like lipocalin Homo sapiens Human Zinc finger protein 250 Zinc finger protein 647 Homo sapiens Human Arginine-glutamic acid dipeptide repeats protein Atrophin 1 like protein Atrophin 1 related protein Homo sapiens Human Zinc finger protein 250 Zinc finger protein 647 Homo sapiens Human Arginine-glutamic acid dipeptide repeats protein Atrophin 1 like protein Atrophin 1 related protein Homo sapiens Human Arginine-glutamic acid dipeptide repeats protein Atrophin 1 like protein Atrophin 1 related protein Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human Nuclear pore complex protein Nup153 Nucleoporin Nup153 153 kDa nucleoporin Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human Olfactory receptor 51G1 Homo sapiens Human Bcl-2-modifying factor Homo sapiens Human Mitochondrial intermediate peptidase mitochondrial precursor EC 3 4 24 59 MIP Homo sapiens Human 4 599 555 713 480 283 283 283 849 621 807 728 715 684 446 896 548 1023 1035 392 392 263 263 571 254 254 699 648 761 131 1 65 2 15.73 66 67 15.58 15.48 68 69 15.14 14.77 70 14.77 71 72 14.71 14.01 73 13.95 74 13.67 75 76 77 78 13.60 13.60 12.98 12.87 79 12.87 80 81 12.51 12.12 82 12.06 83 84 11.90 11.85 85 86 87 11.59 11.59 11.56 88 11.56 3 Actin-binding Rho activating protein Striated muscle activator of Rho dependent signaling STARS Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human Cadherin-like protein 26 precursor Cadherin like protein VR20 Homo sapiens Human Bcl-2-modifying factor Homo sapiens Human Complex I intermediate associated protein 30 mitochondrial precursor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly factor 1 Homo sapiens Human Complex I intermediate associated protein 30 mitochondrial precursor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly factor 1 Homo sapiens Human Bcl-2-modifying factor Homo sapiens Human Actin-binding Rho activating protein Striated muscle activator of Rho dependent signaling STARS Homo sapiens Human Immunoglobulin superfamily member 8 precursor CD81 partner 3 Glu Trp Ile EWI motif containing protein 2 EWI 2 Keratinocytes associated transmembrane protein 4 KCT 4 LIR D1 CD316 antigen Homo sapiens Human Prolargin precursor Proline arginine rich end leucine rich repeat protein Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human Uncharacterized protein C9orf79 Homo sapiens Human Arginine-glutamic acid dipeptide repeats protein Atrophin 1 like protein Atrophin 1 related protein Homo sapiens Human Arginine-glutamic acid dipeptide repeats protein Atrophin 1 like protein Atrophin 1 related protein Homo sapiens Human HpaII tiny fragments locus 9c protein Homo sapiens Human Immunoglobulin superfamily member 8 precursor CD81 partner 3 Glu Trp Ile EWI motif containing protein 2 EWI 2 Keratinocytes associated transmembrane protein 4 KCT 4 LIR D1 CD316 antigen Homo sapiens Human Immunoglobulin superfamily member 8 precursor CD81 partner 3 Glu Trp Ile EWI motif containing protein 2 EWI 2 Keratinocytes associated transmembrane protein 4 KCT 4 LIR D1 CD316 antigen Homo sapiens Human Uncharacterized protein KIAA0196 Homo sapiens Human FYN-binding protein FYN T binding protein FYB 120 130 p120 p130 SLP 76 associated phosphoprotein SLAP 130 Adhesion and degranulation promoting adaptor protein ADAP Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human Complex I intermediate associated protein 30 mitochondrial precursor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly factor 1 Homo sapiens Human Complex I intermediate associated protein 30 mitochondrial precursor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly factor 1 Homo sapiens Human 4 600 650 763 559 355 355 665 513 512 717 257 257 558 377 377 782 582 743 508 606 302 302 247 247 132 1 89 90 2 11.40 11.22 91 92 93 94 95 11.19 11.19 11.02 11.00 10.99 96 10.99 97 10.87 98 10.87 99 10.77 100 10.74 101 102 103 104 10.67 10.64 10.55 10.54 105 10.26 106 10.06 107 9.90 108 109 9.90 9.79 110 111 9.64 9.59 112 113 114 115 116 117 118 119 120 9.57 9.57 9.45 9.43 9.37 9.37 9.36 9.36 9.28 121 122 9.21 9.10 3 Uncharacterized protein C9orf79 Homo sapiens Human E3 ubiquitin protein ligase RNF19 EC 6 3 2 RING finger protein 19 Dorfin Double ring finger protein p38 protein Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human Bcl-2-modifying factor Homo sapiens Human Zinc finger BED domain containing protein 4 Homo sapiens Human Arginine-glutamic acid dipeptide repeats protein Atrophin 1 like protein Atrophin 1 related protein Homo sapiens Human Arginine-glutamic acid dipeptide repeats protein Atrophin 1 like protein Atrophin 1 related protein Homo sapiens Human Cadherin-like protein 26 precursor Cadherin like protein VR20 Homo sapiens Human Cadherin-like protein 26 precursor Cadherin like protein VR20 Homo sapiens Human Zinc finger protein 295 Zinc finger and BTB domain containing protein 21 Homo sapiens Human Zinc finger protein 250 Zinc finger protein 647 Homo sapiens Human E3 Angiopoietin-1 precursor ANG 1 Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human Nuclear pore complex protein Nup153 Nucleoporin Nup153 153 kDa nucleoporin Homo sapiens Human Anaphase-promoting complex subunit 2 APC2 Cyclosome subunit 2 Homo sapiens Human Nuclear pore complex protein Nup153 Nucleoporin Nup153 153 kDa nucleoporin Homo sapiens Human Zinc finger protein 250 Zinc finger protein 647 Homo sapiens Human Zinc finger protein 250 Zinc finger protein 647 Homo sapiens Human Nuclear pore complex protein Nup153 Nucleoporin Nup153 153 kDa nucleoporin Homo sapiens Human Glial fibrillary acidic protein astrocyte GFAP Homo sapiens Human Arginine-glutamic acid dipeptide repeats protein Atrophin 1 like protein Atrophin 1 related protein Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human Frizzled-2 precursor Fz 2 hFz2 FzE2 Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human Cathepsin S precursor EC 3 4 22 27 Homo sapiens Human Cathepsin S precursor EC 3 4 22 27 Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human Telomeric repeat binding factor 2 TTAGGG repeat binding factor 2 Telomeric DNA binding protein Homo sapiens Human Uncharacterized protein C9orf79 Homo sapiens Human Beta-defensin 118 precursor Defensin beta 118 Beta defensin 18 DEFB 18 Epididymal secretory protein 13 6 ESP13 6 Homo sapiens Human 4 494 601 252 252 646 484 359 359 376 376 752 608 997 467 958 553 836 514 542 542 636 562 466 285 285 711 934 239 239 289 289 637 724 841 133 1 123 124 125 126 2 9.01 9.01 8.82 8.69 127 8.69 128 8.68 129 8.60 130 8.60 131 8.55 132 8.55 133 134 135 136 8.46 8.18 8.18 8.10 137 138 139 140 141 142 143 8.00 8.00 7.99 7.95 7.90 7.90 7.88 144 7.88 145 7.86 146 7.86 147 7.84 148 7.84 149 7.84 150 7.77 3 4 Keratin-associated protein 21 2 Homo sapiens Human 246 Keratin-associated protein 21 2 Homo sapiens Human 246 Uncharacterized protein C18orf54 precursor Homo sapiens Human 472 Nuclear pore complex protein Nup153 Nucleoporin Nup153 153 400 kDa nucleoporin Homo sapiens Human Nuclear pore complex protein Nup153 Nucleoporin Nup153 153 400 kDa nucleoporin Homo sapiens Human Vacuolar protein sorting associated protein 25 hVps25 ELL asso1033 ciated protein of 20 kDa Dermal papilla derived protein 9 Homo sapiens Human Complex I intermediate associated protein 30 mitochondrial precur232 sor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly factor 1 Homo sapiens Human Complex I intermediate associated protein 30 mitochondrial precur232 sor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly factor 1 Homo sapiens Human Cadherin-like protein 26 precursor Cadherin like protein VR20 Ho371 mo sapiens Human Cadherin-like protein 26 precursor Cadherin like protein VR20 Ho371 mo sapiens Human Bcl-2-modifying factor Homo sapiens Human 428 Keratin-associated protein 21 2 Homo sapiens Human 277 Keratin-associated protein 21 2 Homo sapiens Human 277 Olfactory receptor 10A7 Olfactory receptor OR12 6 Homo sapiens 1024 Human Keratin-associated protein 21 2 Homo sapiens Human 275 Keratin-associated protein 21 2 Homo sapiens Human 275 Zinc finger protein 225 Homo sapiens Human 420 Keratin-associated protein 21 2 Homo sapiens Human 975 Angiopoietin-1 precursor ANG 1 Homo sapiens Human 344 Angiopoietin-1 precursor ANG 1 Homo sapiens Human 344 Arginine-glutamic acid dipeptide repeats protein Atrophin 1 like 381 protein Atrophin 1 related protein Homo sapiens Human Arginine-glutamic acid dipeptide repeats protein Atrophin 1 like 381 protein Atrophin 1 related protein Homo sapiens Human Complex I intermediate associated protein 30 mitochondrial precur320 sor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly factor 1 Homo sapiens Human Complex I intermediate associated protein 30 mitochondrial precur320 sor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly factor 1 Homo sapiens Human Nuclear pore complex protein Nup153 Nucleoporin Nup153 153 408 kDa nucleoporin Homo sapiens Human Nuclear pore complex protein Nup153 Nucleoporin Nup153 153 408 kDa nucleoporin Homo sapiens Human Nuclear pore complex protein Nup153 Nucleoporin Nup153 153 408 kDa nucleoporin Homo sapiens Human Arginine-glutamic acid dipeptide repeats protein Atrophin 1 like 518 protein Atrophin 1 related protein Homo sapiens Human 134 1 151 2 7.74 152 153 7.69 7.66 154 155 156 7.58 7.58 7.57 157 158 159 160 7.47 7.47 7.47 7.29 161 7.29 162 163 7.23 7.13 164 7.10 165 7.09 166 167 7.08 7.05 168 7.05 169 7.02 170 6.98 171 6.98 172 6.95 173 6.95 174 6.88 175 6.72 3 Vacuolar ATP synthase subunit G 2 EC 3 6 3 14 V ATPase G subunit 2 Vacuolar proton pump G subunit 2 V ATPase 13 kDa subunit 2 Homo sapiens Human Bcl-2-modifying factor Homo sapiens Human Vacuolar protein sorting associated protein 25 hVps25 ELL associated protein of 20 kDa Dermal papilla derived protein 9 Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human MANSC domain containing protein 1 precursor Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human Telomeric repeat binding factor 2 TTAGGG repeat binding factor 2 Telomeric DNA binding protein Homo sapiens Human Telomeric repeat binding factor 2 TTAGGG repeat binding factor 2 Telomeric DNA binding protein Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human Zinc finger and BTB domain containing protein 41 Homo sapiens Human Arginine-glutamic acid dipeptide repeats protein Atrophin 1 like protein Atrophin 1 related protein Homo sapiens Human Olfactory receptor 10A7 Olfactory receptor OR12 6 Homo sapiens Human Bcl-2-modifying factor Homo sapiens Human Putative tyrosine protein phosphatase TPTE EC 3 1 3 48 Transmembrane phosphatase with tensin homology Protein BJ HCC 5 Homo sapiens Human Putative tyrosine protein phosphatase TPTE EC 3 1 3 48 Transmembrane phosphatase with tensin homology Protein BJ HCC 5 Homo sapiens Human Transcription factor MafK Erythroid transcription factor NF E2 p18 subunit Homo sapiens Human Brevican core protein precursor Brain enriched hyaluronan binding protein Protein BEHAB Homo sapiens Human Brevican core protein precursor Brain enriched hyaluronan binding protein Protein BEHAB Homo sapiens Human Complex I intermediate associated protein 30 mitochondrial precursor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly factor 1 Homo sapiens Human Complex I intermediate associated protein 30 mitochondrial precursor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly factor 1 Homo sapiens Human Arginine-glutamic acid dipeptide repeats protein Atrophin 1 like protein Atrophin 1 related protein Homo sapiens Human Complex I intermediate associated protein 30 mitochondrial precursor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly factor 1 Homo sapiens Human 4 776 457 410 290 290 892 305 305 305 405 405 944 923 516 917 953 388 388 766 409 409 351 351 488 368 135 1 176 2 6.72 177 178 179 180 6.71 6.71 6.71 6.66 181 6.64 182 183 184 6.57 6.57 6.50 185 6.50 186 6.46 187 6.43 188 6.43 189 190 6.33 6.31 191 6.31 192 6.31 193 6.25 194 6.25 195 6.20 196 6.20 197 6.17 198 6.09 199 200 201 6.08 5.95 5.93 202 5.93 3 4 Complex I intermediate associated protein 30 mitochondrial precur368 sor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly factor 1 Homo sapiens Human Zinc finger BED domain containing protein 4 Homo sapiens Human 380 Zinc finger BED domain containing protein 4 Homo sapiens Human 380 Zinc finger BED domain containing protein 4 Homo sapiens Human 380 Epididymal-specific lipocalin 9 precursor MUP like lipocalin Homo 797 sapiens Human Beta-defensin 118 precursor Defensin beta 118 Beta defensin 18 771 DEFB 18 Epididymal secretory protein 13 6 ESP13 6 Homo sapiens Human Angiopoietin-1 precursor ANG 1 Homo sapiens Human 328 Angiopoietin-1 precursor ANG 1 Homo sapiens Human 328 Zinc finger protein 250 Zinc finger protein 647 Homo sapiens Hu725 man Zinc finger protein 250 Zinc finger protein 647 Homo sapiens Hu725 man Arginine-glutamic acid dipeptide repeats protein Atrophin 1 like 425 protein Atrophin 1 related protein Homo sapiens Human Complex I intermediate associated protein 30 mitochondrial precur379 sor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly factor 1 Homo sapiens Human Complex I intermediate associated protein 30 mitochondrial precur379 sor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly factor 1 Homo sapiens Human Uncharacterized protein C18orf54 precursor Homo sapiens Human 492 Telomeric repeat binding factor 2 TTAGGG repeat binding factor 2 406 Telomeric DNA binding protein Homo sapiens Human Telomeric repeat binding factor 2 TTAGGG repeat binding factor 2 406 Telomeric DNA binding protein Homo sapiens Human Telomeric repeat binding factor 2 TTAGGG repeat binding factor 2 406 Telomeric DNA binding protein Homo sapiens Human Arginine-glutamic acid dipeptide repeats protein Atrophin 1 like 397 protein Atrophin 1 related protein Homo sapiens Human Arginine-glutamic acid dipeptide repeats protein Atrophin 1 like 397 protein Atrophin 1 related protein Homo sapiens Human Zinc finger protein ZFPM2 Zinc finger protein multitype 2 Friend of 231 GATA protein 2 FOG 2 hFOG 2 Homo sapiens Human Zinc finger protein ZFPM2 Zinc finger protein multitype 2 Friend of 231 GATA protein 2 FOG 2 hFOG 2 Homo sapiens Human Nuclear pore complex protein Nup153 Nucleoporin Nup153 153 634 kDa nucleoporin Homo sapiens Human PHD finger protein 21A BRAF35 HDAC complex protein BHC80 1039 BHC80a Homo sapiens Human Biotinidase precursor EC 3 5 1 12 Homo sapiens Human 915 Secretagogin Homo sapiens Human 946 Zinc finger protein 250 Zinc finger protein 647 Homo sapiens Hu573 man Zinc finger protein 250 Zinc finger protein 647 Homo sapiens Hu573 man 136 1 203 2 5.86 204 205 206 207 5.84 5.79 5.79 5.78 208 5.78 209 5.76 210 5.72 211 5.72 212 5.70 213 5.70 214 5.67 215 216 5.66 5.59 217 218 5.58 5.51 219 5.51 220 5.50 221 5.42 222 5.39 223 5.38 224 225 226 227 228 229 5.36 5.36 5.35 5.35 5.34 5.32 3 4 Complex I intermediate associated protein 30 mitochondrial precur677 sor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly factor 1 Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human 688 Keratin-associated protein 21 2 Homo sapiens Human 644 Keratin-associated protein 21 2 Homo sapiens Human 644 Complex I intermediate associated protein 30 mitochondrial precur297 sor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly factor 1 Homo sapiens Human Complex I intermediate associated protein 30 mitochondrial precur297 sor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly factor 1 Homo sapiens Human Hepatocyte nuclear factor 3 alpha HNF 3A Forkhead box protein A1 867 Homo sapiens Human Nuclear pore complex protein Nup153 Nucleoporin Nup153 153 363 kDa nucleoporin Homo sapiens Human Nuclear pore complex protein Nup153 Nucleoporin Nup153 153 363 kDa nucleoporin Homo sapiens Human Complex I intermediate associated protein 30 mitochondrial precur308 sor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly factor 1 Homo sapiens Human Complex I intermediate associated protein 30 mitochondrial precur308 sor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly factor 1 Homo sapiens Human Zinc finger protein 250 Zinc finger protein 647 Homo sapiens Hu703 man Keratin-associated protein 21 2 Homo sapiens Human 855 Cytochrome P450 2W1 EC 1 14 14 CYPIIW1 Homo sapiens Hu770 man Immunoglobulin J chain Homo sapiens Human 887 Sulfhydryl oxidase 1 precursor EC 1 8 3 2 Quiescin Q6 hQSOX 504 Homo sapiens Human Sulfhydryl oxidase 1 precursor EC 1 8 3 2 Quiescin Q6 hQSOX 504 Homo sapiens Human Nuclear pore complex protein Nup153 Nucleoporin Nup153 153 757 kDa nucleoporin Homo sapiens Human Telomeric repeat binding factor 2 TTAGGG repeat binding factor 2 614 Telomeric DNA binding protein Homo sapiens Human Serine/threonine-protein kinase 17B EC 2 7 11 1 DAP kinase related 858 apoptosis inducing protein kinase 2 Homo sapiens Human Group IIF secretory phospholipase A2 precursor EC 3 1 1 4 Phos881 phatidylcholine 2 acylhydrolase GIIF GIIF sPLA2 sPLA 2 IIF Homo sapiens Human Bcl-2-modifying factor Homo sapiens Human 546 Bcl-2-modifying factor Homo sapiens Human 546 Keratin-associated protein 21 2 Homo sapiens Human 286 Keratin-associated protein 21 2 Homo sapiens Human 286 Zinc finger protein 250 Zinc finger protein 647 Homo sapiens Human 1042 Olfactory receptor 10A7 Olfactory receptor OR12 6 Homo sapiens 435 Human 137 1 230 2 5.32 231 5.31 232 5.31 233 5.30 234 5.30 235 5.30 236 5.29 237 5.24 238 5.12 239 5.12 240 5.11 241 5.10 242 5.07 243 5.07 244 5.04 245 246 247 5.02 5.02 4.99 248 4.97 249 4.96 250 4.96 251 252 253 4.95 4.95 4.86 3 Olfactory receptor 10A7 Olfactory receptor OR12 6 Homo sapiens Human Actin-binding Rho activating protein Striated muscle activator of Rho dependent signaling STARS Homo sapiens Human Actin-binding Rho activating protein Striated muscle activator of Rho dependent signaling STARS Homo sapiens Human Nuclear pore complex protein Nup153 Nucleoporin Nup153 153 kDa nucleoporin Homo sapiens Human Nuclear pore complex protein Nup153 Nucleoporin Nup153 153 kDa nucleoporin Homo sapiens Human Nuclear pore complex protein Nup153 Nucleoporin Nup153 153 kDa nucleoporin Homo sapiens Human Complex I intermediate associated protein 30 mitochondrial precursor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly factor 1 Homo sapiens Human Nuclear pore complex protein Nup153 Nucleoporin Nup153 153 kDa nucleoporin Homo sapiens Human Complex I intermediate associated protein 30 mitochondrial precursor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly factor 1 Homo sapiens Human Complex I intermediate associated protein 30 mitochondrial precursor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly factor 1 Homo sapiens Human Actin-binding Rho activating protein Striated muscle activator of Rho dependent signaling STARS Homo sapiens Human PHD finger protein 21A BRAF35 HDAC complex protein BHC80 BHC80a Homo sapiens Human Complex I intermediate associated protein 30 mitochondrial precursor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly factor 1 Homo sapiens Human Complex I intermediate associated protein 30 mitochondrial precursor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly factor 1 Homo sapiens Human Syntaxin-binding protein 1 Unc 18 homolog Unc 18A Unc 18 1 N Sec1 p67 Homo sapiens Human Bifunctional Bifunctional Cadherin-like protein 26 precursor Cadherin like protein VR20 Homo sapiens Human Arginine-glutamic acid dipeptide repeats protein Atrophin 1 like protein Atrophin 1 related protein Homo sapiens Human Inositol polyphosphate multikinase EC 2 7 1 151 Inositol 1 3 4 6 tetrakisphosphate 5 kinase Homo sapiens Human Inositol polyphosphate multikinase EC 2 7 1 151 Inositol 1 3 4 6 tetrakisphosphate 5 kinase Homo sapiens Human Zinc finger protein 225 Homo sapiens Human Zinc finger protein 225 Homo sapiens Human Mitogen-activated protein kinase kinase kinase 15 EC 2 7 11 25 MAPK ERK kinase kinase 15 MEK kinase 15 MEKK 15 Homo sapiens Human 4 435 499 499 401 401 401 523 768 343 343 638 723 864 864 412 260 260 720 575 398 398 541 541 809 138 1 254 2 4.77 255 4.76 256 257 4.71 4.70 258 259 260 261 262 263 264 265 4.68 4.62 4.62 4.62 4.62 4.62 4.62 4.61 266 4.60 267 4.60 268 4.59 269 4.57 270 271 272 273 4.56 4.56 4.56 4.50 274 4.50 275 4.47 276 4.43 277 4.43 278 4.43 279 4.42 280 4.39 281 282 283 4.37 4.37 4.29 3 4 Cadherin-like protein 26 precursor Cadherin like protein VR20 Ho707 mo sapiens Human Olfactory receptor 10A7 Olfactory receptor OR12 6 Homo sapiens 900 Human Bcl-2-modifying factor Homo sapiens Human 655 Olfactory receptor 10A7 Olfactory receptor OR12 6 Homo sapiens 1025 Human Bcl-2-modifying factor Homo sapiens Human 628 Keratin-associated protein 21 2 Homo sapiens Human 251 Keratin-associated protein 21 2 Homo sapiens Human 251 Keratin-associated protein 21 2 Homo sapiens Human 251 Keratin-associated protein 21 2 Homo sapiens Human 251 Keratin-associated protein 21 2 Homo sapiens Human 251 Keratin-associated protein 21 2 Homo sapiens Human 251 Zinc finger protein 250 Zinc finger protein 647 Homo sapiens Hu565 man Arginine-glutamic acid dipeptide repeats protein Atrophin 1 like 386 protein Atrophin 1 related protein Homo sapiens Human Arginine-glutamic acid dipeptide repeats protein Atrophin 1 like 386 protein Atrophin 1 related protein Homo sapiens Human Zinc finger protein 96 Zinc finger protein 305 Zinc finger and SCAN 779 domain containing protein 12 Homo sapiens Human Arginine-glutamic acid dipeptide repeats protein Atrophin 1 like 423 protein Atrophin 1 related protein Homo sapiens Human Zinc finger protein 677 Homo sapiens Human 517 Zinc finger protein 677 Homo sapiens Human 517 Zinc finger protein 677 Homo sapiens Human 517 Regenerating islet derived protein 4 precursor Reg IV REG like 327 protein Gastrointestinal secretory protein Homo sapiens Human Regenerating islet derived protein 4 precursor Reg IV REG like 327 protein Gastrointestinal secretory protein Homo sapiens Human Serine/threonine-protein kinase VRK1 EC 2 7 11 1 Vaccinia related 778 kinase 1 Homo sapiens Human Complex I intermediate associated protein 30 mitochondrial precur248 sor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly factor 1 Homo sapiens Human Complex I intermediate associated protein 30 mitochondrial precur248 sor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly factor 1 Homo sapiens Human Complex I intermediate associated protein 30 mitochondrial precur248 sor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly factor 1 Homo sapiens Human Arginine-glutamic acid dipeptide repeats protein Atrophin 1 like 586 protein Atrophin 1 related protein Homo sapiens Human Keratin, type I cytoskeletal 9 Cytokeratin 9 CK 9 Keratin 9 K9 Ho1032 mo sapiens Human Ig lambda chain V II region TRO Homo sapiens Human 603 Ig lambda chain V II region TRO Homo sapiens Human 603 Zinc finger protein 250 Zinc finger protein 647 Homo sapiens Hu552 man 139 1 284 285 286 287 2 4.28 4.27 4.27 4.26 288 4.26 289 4.23 290 4.22 291 4.22 292 4.19 293 4.19 294 4.18 295 296 297 4.17 4.13 4.12 298 4.12 299 300 4.11 4.09 301 302 303 304 305 4.08 4.08 4.08 4.08 4.03 306 4.02 307 308 309 3.98 3.98 3.97 3 Oligodendrocyte transcription factor 1 Oligo1 Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human Regenerating islet derived protein 4 precursor Reg IV REG like protein Gastrointestinal secretory protein Homo sapiens Human Regenerating islet derived protein 4 precursor Reg IV REG like protein Gastrointestinal secretory protein Homo sapiens Human Arginine-glutamic acid dipeptide repeats protein Atrophin 1 like protein Atrophin 1 related protein Homo sapiens Human Complex I intermediate associated protein 30 mitochondrial precursor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly factor 1 Homo sapiens Human Complex I intermediate associated protein 30 mitochondrial precursor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly factor 1 Homo sapiens Human Complex I intermediate associated protein 30 mitochondrial precursor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly factor 1 Homo sapiens Human Complex I intermediate associated protein 30 mitochondrial precursor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly factor 1 Homo sapiens Human Cadherin-like protein 26 precursor Cadherin like protein VR20 Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human Bcl-2-modifying factor Homo sapiens Human Complex I intermediate associated protein 30 mitochondrial precursor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly factor 1 Homo sapiens Human Complex I intermediate associated protein 30 mitochondrial precursor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly factor 1 Homo sapiens Human Uncharacterized protein C21orf62 B37 Homo sapiens Human Vacuolar protein sorting associated protein 25 hVps25 ELL associated protein of 20 kDa Dermal papilla derived protein 9 Homo sapiens Human Profilin-3 Profilin III Homo sapiens Human Profilin-3 Profilin III Homo sapiens Human Profilin-3 Profilin III Homo sapiens Human Profilin-3 Profilin III Homo sapiens Human Vacuolar ATP synthase subunit G 2 EC 3 6 3 14 V ATPase G subunit 2 Vacuolar proton pump G subunit 2 V ATPase 13 kDa subunit 2 Homo sapiens Human Trans-Golgi network integral membrane protein 2 precursor Trans Golgi network protein TGN51 TGN46 TGN48 TGN38 homolog Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human Complex I intermediate associated protein 30 mitochondrial precursor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly factor 1 Homo sapiens Human 4 427 300 300 259 259 647 676 676 374 374 589 679 765 326 326 416 476 244 244 244 244 824 829 976 976 390 140 1 310 2 3.97 311 3.97 312 3.96 313 3.96 314 3.94 315 3.94 316 3.92 317 3.92 318 3.92 319 3.90 320 3.90 321 3.87 322 3.87 323 324 3.85 3.80 325 3.75 326 3.73 327 3.71 328 3.71 329 3.71 330 3.67 331 3.65 3 4 Complex I intermediate associated protein 30 mitochondrial precur390 sor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly factor 1 Homo sapiens Human Complex I intermediate associated protein 30 mitochondrial precur390 sor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly factor 1 Homo sapiens Human Olfactory receptor 10A7 Olfactory receptor OR12 6 Homo sapiens 954 Human Olfactory receptor 10A7 Olfactory receptor OR12 6 Homo sapiens 954 Human Presequence protease mitochondrial precursor EC 3 4 24 hPreP 407 Pitrilysin metalloproteinase 1 Metalloprotease 1 hMP1 Homo sapiens Human Presequence protease mitochondrial precursor EC 3 4 24 hPreP 407 Pitrilysin metalloproteinase 1 Metalloprotease 1 hMP1 Homo sapiens Human Cadherin-like protein 26 precursor Cadherin like protein VR20 Ho572 mo sapiens Human Cadherin-like protein 26 precursor Cadherin like protein VR20 Ho572 mo sapiens Human Cadherin-like protein 26 precursor Cadherin like protein VR20 Ho572 mo sapiens Human Zinc finger protein 250 Zinc finger protein 647 Homo sapiens Hu631 man Zinc finger protein 250 Zinc finger protein 647 Homo sapiens Hu631 man Complex I intermediate associated protein 30 mitochondrial precur340 sor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly factor 1 Homo sapiens Human Complex I intermediate associated protein 30 mitochondrial precur340 sor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly factor 1 Homo sapiens Human Glial fibrillary acidic protein astrocyte GFAP Homo sapiens Human 460 Arginine-glutamic acid dipeptide repeats protein Atrophin 1 like 566 protein Atrophin 1 related protein Homo sapiens Human Arginine-glutamic acid dipeptide repeats protein Atrophin 1 like 712 protein Atrophin 1 related protein Homo sapiens Human Complex I intermediate associated protein 30 mitochondrial precur463 sor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly factor 1 Homo sapiens Human Zinc finger protein 250 Zinc finger protein 647 Homo sapiens Hu337 man Zinc finger protein 250 Zinc finger protein 647 Homo sapiens Hu337 man Zinc finger protein 250 Zinc finger protein 647 Homo sapiens Hu337 man Keratin, type I cytoskeletal 9 Cytokeratin 9 CK 9 Keratin 9 K9 Ho1016 mo sapiens Human Microtubule-associated protein 9 Aster associated protein Homo 240 sapiens Human 141 1 332 2 3.65 333 334 3.62 3.61 335 3.61 336 3.60 337 3.60 338 3.60 339 3.59 340 3.59 341 3.59 342 3.58 343 344 345 346 347 3.55 3.54 3.54 3.53 3.51 348 3.50 349 3.50 350 3.49 351 3.49 352 3.49 353 3.47 354 3.47 355 356 3.46 3.44 357 3.44 3 Microtubule-associated protein 9 Aster associated protein Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human Ubiquitin carboxyl terminal hydrolase 42 EC 3 1 2 15 Ubiquitin thioesterase 42 Ubiquitin specific processing protease 42 Deubiquitinating enzyme 42 Homo sapiens Human Ubiquitin carboxyl terminal hydrolase 42 EC 3 1 2 15 Ubiquitin thioesterase 42 Ubiquitin specific processing protease 42 Deubiquitinating enzyme 42 Homo sapiens Human PR domain zinc finger protein 6 PR domain containing protein 6 Fragment Homo sapiens Human PR domain zinc finger protein 6 PR domain containing protein 6 Fragment Homo sapiens Human PR domain zinc finger protein 6 PR domain containing protein 6 Fragment Homo sapiens Human Regenerating islet derived protein 4 precursor Reg IV REG like protein Gastrointestinal secretory protein Homo sapiens Human Regenerating islet derived protein 4 precursor Reg IV REG like protein Gastrointestinal secretory protein Homo sapiens Human Regenerating islet derived protein 4 precursor Reg IV REG like protein Gastrointestinal secretory protein Homo sapiens Human Zinc finger protein 250 Zinc finger protein 647 Homo sapiens Human Zinc finger protein 225 Homo sapiens Human Transmembrane protein 106B Homo sapiens Human Transmembrane protein 106B Homo sapiens Human Chloride channel protein 6 ClC 6 Homo sapiens Human Regenerating islet derived protein 4 precursor Reg IV REG like protein Gastrointestinal secretory protein Homo sapiens Human Complex I intermediate associated protein 30 mitochondrial precursor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly factor 1 Homo sapiens Human Complex I intermediate associated protein 30 mitochondrial precursor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly factor 1 Homo sapiens Human Olfactory receptor 10A7 Olfactory receptor OR12 6 Homo sapiens Human Olfactory receptor 10A7 Olfactory receptor OR12 6 Homo sapiens Human Olfactory receptor 10A7 Olfactory receptor OR12 6 Homo sapiens Human Regenerating islet derived protein 4 precursor Reg IV REG like protein Gastrointestinal secretory protein Homo sapiens Human Regenerating islet derived protein 4 precursor Reg IV REG like protein Gastrointestinal secretory protein Homo sapiens Human Bcl-2-modifying factor Homo sapiens Human Regenerating islet derived protein 4 precursor Reg IV REG like protein Gastrointestinal secretory protein Homo sapiens Human Regenerating islet derived protein 4 precursor Reg IV REG like protein Gastrointestinal secretory protein Homo sapiens Human 4 240 651 438 438 578 578 578 324 324 324 464 418 375 375 842 888 318 318 316 316 316 323 323 747 315 315 142 1 358 2 3.44 359 3.43 360 3.43 361 3.42 362 3.42 363 3.42 364 3.42 365 3.40 366 3.40 367 3.39 368 3.38 369 370 371 3.37 3.37 3.35 372 373 3.33 3.32 374 3.32 375 376 3.31 3.30 377 3.30 378 3.30 379 3.29 380 3.29 381 3.27 382 3.26 383 3.26 3 Regenerating islet derived protein 4 precursor Reg IV REG like protein Gastrointestinal secretory protein Homo sapiens Human Actin-binding Rho activating protein Striated muscle activator of Rho dependent signaling STARS Homo sapiens Human Actin-binding Rho activating protein Striated muscle activator of Rho dependent signaling STARS Homo sapiens Human Regenerating islet derived protein 4 precursor Reg IV REG like protein Gastrointestinal secretory protein Homo sapiens Human Regenerating islet derived protein 4 precursor Reg IV REG like protein Gastrointestinal secretory protein Homo sapiens Human Regenerating islet derived protein 4 precursor Reg IV REG like protein Gastrointestinal secretory protein Homo sapiens Human Regenerating islet derived protein 4 precursor Reg IV REG like protein Gastrointestinal secretory protein Homo sapiens Human Inositol polyphosphate multikinase EC 2 7 1 151 Inositol 1 3 4 6 tetrakisphosphate 5 kinase Homo sapiens Human Inositol polyphosphate multikinase EC 2 7 1 151 Inositol 1 3 4 6 tetrakisphosphate 5 kinase Homo sapiens Human Ligand-dependent corepressor LCoR Mblk1 related protein 2 Homo sapiensHuman B-lymphocyte antigen CD19 precursor Differentiation antigen CD19 B lymphocyte surface antigen B4 Leu 12 Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human Kinesin-like protein KIF3A Microtubule plus end directed kinesin motor 3A Homo sapiens Human Protein yippee like 4 Homo sapiens Human Zinc finger protein 250 Zinc finger protein 647 Homo sapiens Human Zinc finger protein 250 Zinc finger protein 647 Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human Regenerating islet derived protein 4 precursor Reg IV REG like protein Gastrointestinal secretory protein Homo sapiens Human Regenerating islet derived protein 4 precursor Reg IV REG like protein Gastrointestinal secretory protein Homo sapiens Human Regenerating islet derived protein 4 precursor Reg IV REG like protein Gastrointestinal secretory protein Homo sapiens Human Regenerating islet derived protein 4 precursor Reg IV REG like protein Gastrointestinal secretory protein Homo sapiens Human Regenerating islet derived protein 4 precursor Reg IV REG like protein Gastrointestinal secretory protein Homo sapiens Human Regenerating islet derived protein 4 precursor Reg IV REG like protein Gastrointestinal secretory protein Homo sapiens Human Complex I intermediate associated protein 30 mitochondrial precursor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly factor 1 Homo sapiens Human Complex I intermediate associated protein 30 mitochondrial precursor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly factor 1 Homo sapiens Human 4 315 758 758 296 296 296 296 602 602 952 962 701 701 882 880 570 570 933 279 279 279 661 661 908 335 335 143 1 384 385 386 387 388 2 3.25 3.25 3.25 3.25 3.23 389 3.23 390 3.22 391 3.20 392 3.20 393 3.20 394 3.20 395 3.20 396 397 3.19 3.18 398 3.18 399 3.18 400 3.18 401 3.17 402 3.17 403 3.17 404 3.16 405 3.16 3 Keratin-associated protein 21 2 Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human Zinc finger protein 295 Zinc finger and BTB domain containing protein 21 Homo sapiens Human Zinc finger protein 295 Zinc finger and BTB domain containing protein 21 Homo sapiens Human Rho guanine nucleotide exchange factor 5 Guanine nucleotide regulatory protein TIM Oncogene TIM p60 TIM Transforming immortalized mammary oncogene Homo sapiens Human Complex I intermediate associated protein 30 mitochondrial precursor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly factor 1 Homo sapiens Human Complex I intermediate associated protein 30 mitochondrial precursor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly factor 1 Homo sapiens Human Complex I intermediate associated protein 30 mitochondrial precursor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly factor 1 Homo sapiens Human Complex I intermediate associated protein 30 mitochondrial precursor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly factor 1 Homo sapiens Human Complex I intermediate associated protein 30 mitochondrial precursor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly factor 1 Homo sapiens Human MARVEL domain containing protein 1 Homo sapiens Human Ladinin 1 Lad 1 120 kDa linear IgA bullous dermatosis antigen 97 kDa linear IgA bullous dermatosis antigen Linear IgA disease antigen homolog LadA Homo sapiens Human Ladinin 1 Lad 1 120 kDa linear IgA bullous dermatosis antigen 97 kDa linear IgA bullous dermatosis antigen Linear IgA disease antigen homolog LadA Homo sapiens Human Ladinin 1 Lad 1 120 kDa linear IgA bullous dermatosis antigen 97 kDa linear IgA bullous dermatosis antigen Linear IgA disease antigen homolog LadA Homo sapiens Human Ladinin 1 Lad 1 120 kDa linear IgA bullous dermatosis antigen 97 kDa linear IgA bullous dermatosis antigen Linear IgA disease antigen homolog LadA Homo sapiens Human Regenerating islet derived protein 4 precursor Reg IV REG like protein Gastrointestinal secretory protein Homo sapiens Human Regenerating islet derived protein 4 precursor Reg IV REG like protein Gastrointestinal secretory protein Homo sapiens Human Regenerating islet derived protein 4 precursor Reg IV REG like protein Gastrointestinal secretory protein Homo sapiens Human Arginine-glutamic acid dipeptide repeats protein Atrophin 1 like protein Atrophin 1 related protein Homo sapiens Human Arginine-glutamic acid dipeptide repeats protein Atrophin 1 like protein Atrophin 1 related protein Homo sapiens Human 4 226 226 226 226 426 426 592 309 309 309 309 309 948 396 396 396 396 356 356 356 429 429 144 1 406 2 3.13 407 3.12 408 3.08 409 410 411 412 3.07 3.07 3.07 3.03 413 414 3.01 3.00 415 3.00 416 2.98 417 2.98 418 2.97 419 2.93 420 2.92 421 2.92 422 2.89 423 2.89 424 2.89 425 2.89 426 2.89 427 428 2.88 2.87 3 4 Teratocarcinoma-derived growth factor 1 precursor Epidermal 982 growth factor like cripto protein CR1 Cripto 1 growth factor CRGF Homo sapiens Human Nuclear pore complex protein Nup153 Nucleoporin Nup153 153 755 kDa nucleoporin Homo sapiens Human Ladinin 1 Lad 1 120 kDa linear IgA bullous dermatosis antigen 97 531 kDa linear IgA bullous dermatosis antigen Linear IgA disease antigen homolog LadA Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human 270 Keratin-associated protein 21 2 Homo sapiens Human 270 Keratin-associated protein 21 2 Homo sapiens Human 270 Cadherin-like protein 26 precursor Cadherin like protein VR20 Ho440 mo sapiens Human Protein yippee like 4 Homo sapiens Human 434 Complex I intermediate associated protein 30 mitochondrial precur346 sor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly factor 1 Homo sapiens Human Complex I intermediate associated protein 30 mitochondrial precur346 sor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly factor 1 Homo sapiens Human Zona pellucida sperm binding protein 2 precursor Zona pellucida 301 glycoprotein ZP2 Zona pellucida protein A Homo sapiens Human Zona pellucida sperm binding protein 2 precursor Zona pellucida 301 glycoprotein ZP2 Zona pellucida protein A Homo sapiens Human Regenerating islet derived protein 4 precursor Reg IV REG like 671 protein Gastrointestinal secretory protein Homo sapiens Human Cadherin-like protein 26 precursor Cadherin like protein VR20 Ho421 mo sapiens Human Telomeric repeat binding factor 2 TTAGGG repeat binding factor 2 635 Telomeric DNA binding protein Homo sapiens Human Telomeric repeat binding factor 2 TTAGGG repeat binding factor 2 635 Telomeric DNA binding protein Homo sapiens Human Complex I intermediate associated protein 30 mitochondrial precur310 sor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly factor 1 Homo sapiens Human Complex I intermediate associated protein 30 mitochondrial precur310 sor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly factor 1 Homo sapiens Human Complex I intermediate associated protein 30 mitochondrial precur310 sor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly factor 1 Homo sapiens Human Complex I intermediate associated protein 30 mitochondrial precur310 sor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly factor 1 Homo sapiens Human Complex I intermediate associated protein 30 mitochondrial precur310 sor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly factor 1 Homo sapiens Human Protein mago nashi homolog Homo sapiens Human 1046 Lipoma HMGIC fusion partner like 2 protein Homo sapiens Human 470 145 1 429 430 2 2.87 2.86 431 2.86 432 2.86 433 2.85 434 2.84 435 2.84 436 2.81 437 2.81 438 2.80 439 440 441 442 443 2.79 2.79 2.79 2.77 2.75 444 2.75 445 2.73 446 2.72 447 2.71 448 2.70 449 2.69 450 2.69 451 2.67 452 2.67 453 2.66 3 4 Lipoma HMGIC fusion partner like 2 protein Homo sapiens Human 470 Regenerating islet derived protein 4 precursor Reg IV REG like 278 protein Gastrointestinal secretory protein Homo sapiens Human Regenerating islet derived protein 4 precursor Reg IV REG like 278 protein Gastrointestinal secretory protein Homo sapiens Human Regenerating islet derived protein 4 precursor Reg IV REG like 278 protein Gastrointestinal secretory protein Homo sapiens Human Arginine-glutamic acid dipeptide repeats protein Atrophin 1 like 574 protein Atrophin 1 related protein Homo sapiens Human Nuclear pore complex protein Nup153 Nucleoporin Nup153 153 505 kDa nucleoporin Homo sapiens Human Nuclear pore complex protein Nup153 Nucleoporin Nup153 153 505 kDa nucleoporin Homo sapiens Human Regenerating islet derived protein 4 precursor Reg IV REG like 652 protein Gastrointestinal secretory protein Homo sapiens Human Regenerating islet derived protein 4 precursor Reg IV REG like 652 protein Gastrointestinal secretory protein Homo sapiens Human Zinc finger protein 250 Zinc finger protein 647 Homo sapiens Hu482 man Transmembrane protein 106B Homo sapiens Human 436 Transmembrane protein 106B Homo sapiens Human 436 Transmembrane protein 106B Homo sapiens Human 436 Protein mago nashi homolog Homo sapiens Human 991 Inositol polyphosphate multikinase EC 2 7 1 151 Inositol 1 3 4 6 404 tetrakisphosphate 5 kinase Homo sapiens Human Inositol polyphosphate multikinase EC 2 7 1 151 Inositol 1 3 4 6 404 tetrakisphosphate 5 kinase Homo sapiens Human Complex I intermediate associated protein 30 mitochondrial precur525 sor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly factor 1 Homo sapiens Human PHD finger protein 21A BRAF35 HDAC complex protein BHC80 619 BHC80a Homo sapiens Human Zinc finger protein 295 Zinc finger and BTB domain containing 678 protein 21 Homo sapiens Human F-box/WD repeat protein 5 F box and WD 40 domain protein 5 642 Homo sapiens Human Regenerating islet derived protein 4 precursor Reg IV REG like 272 protein Gastrointestinal secretory protein Homo sapiens Human Regenerating islet derived protein 4 precursor Reg IV REG like 272 protein Gastrointestinal secretory protein Homo sapiens Human Complex I intermediate associated protein 30 mitochondrial precur530 sor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly factor 1 Homo sapiens Human Complex I intermediate associated protein 30 mitochondrial precur530 sor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly factor 1 Homo sapiens Human Rho guanine nucleotide exchange factor 5 Guanine nucleotide regu- 1022 latory protein TIM Oncogene TIM p60 TIM Transforming immortalized mammary oncogene Homo sapiens Human 146 1 454 455 2 2.65 2.64 456 457 458 2.63 2.63 2.62 459 2.61 460 2.61 461 2.60 462 463 464 465 466 2.59 2.59 2.59 2.59 2.57 467 468 2.56 2.53 469 2.50 470 471 2.49 2.48 472 2.48 473 2.47 474 2.45 475 2.45 476 2.45 477 478 479 480 481 2.40 2.40 2.39 2.36 2.36 3 Protein mago nashi homolog Homo sapiens Human Nucleolar complex protein 4 homolog NOC4 protein homolog NOC4 like protein Nucleolar complex associated protein 4 like protein Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human Epididymal-specific lipocalin 9 precursor MUP like lipocalin Homo sapiens Human Cadherin-like protein 26 precursor Cadherin like protein VR20 Homo sapiens Human Cadherin-like protein 26 precursor Cadherin like protein VR20 Homo sapiens Human Acetylcholine receptor subunit epsilon precursor Homo sapiens Human Bcl-2-modifying factor Homo sapiens Human Bcl-2-modifying factor Homo sapiens Human Bcl-2-modifying factor Homo sapiens Human Bcl-2-modifying factor Homo sapiens Human Rho guanine nucleotide exchange factor 5 Guanine nucleotide regulatory protein TIM Oncogene TIM p60 TIM Transforming immortalized mammary oncogene Homo sapiens Human Transmembrane protein 106B Homo sapiens Human Sclerostin domain containing protein 1 precursor Ectodermal BMP inhibitor Ectodin Uterine sensitization associated gene 1 protein USAG 1 Homo sapiens Human Hemoglobin subunit gamma 2 Hemoglobin gamma 2 chain Gamma 2 globin Hemoglobin gamma G chain Hb F Ggamma Homo sapiens Human Beta-arrestin-2 Arrestin beta 2 Homo sapiens Human Regenerating islet derived protein 4 precursor Reg IV REG like protein Gastrointestinal secretory protein Homo sapiens Human Regenerating islet derived protein 4 precursor Reg IV REG like protein Gastrointestinal secretory protein Homo sapiens Human Olfactory receptor 10A7 Olfactory receptor OR12 6 Homo sapiens Human Multiple epidermal growth factor like domains 6 precursor EGF like domain containing protein 3 Multiple EGF like domain protein 3 Homo sapiens Human Multiple epidermal growth factor like domains 6 precursor EGF like domain containing protein 3 Multiple EGF like domain protein 3 Homo sapiens Human Multiple epidermal growth factor like domains 6 precursor EGF like domain containing protein 3 Multiple EGF like domain protein 3 Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human Zinc finger BED domain containing protein 4 Homo sapiens Human Angiopoietin-1 precursor ANG 1 Homo sapiens Human Angiopoietin-1 precursor ANG 1 Homo sapiens Human 4 907 893 311 311 828 330 330 750 329 329 329 329 479 990 902 940 687 545 545 1003 373 373 373 670 670 411 459 459 147 1 482 483 484 2 2.35 2.35 2.34 485 2.34 486 2.30 487 2.30 488 2.29 489 2.27 490 2.27 491 2.26 492 2.26 493 2.26 494 2.24 495 2.21 496 2.21 497 2.19 498 499 500 2.16 2.15 2.14 501 2.14 502 2.12 503 2.12 504 2.10 505 2.10 3 Zinc finger BED domain containing protein 4 Homo sapiens Human Zinc finger BED domain containing protein 4 Homo sapiens Human Acyl-CoA-binding domain containing protein 7 Homo sapiens Human Acyl-CoA-binding domain containing protein 7 Homo sapiens Human Complex I intermediate associated protein 30 mitochondrial precursor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly factor 1 Homo sapiens Human Complex I intermediate associated protein 30 mitochondrial precursor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly factor 1 Homo sapiens Human Beta-defensin 118 precursor Defensin beta 118 Beta defensin 18 DEFB 18 Epididymal secretory protein 13 6 ESP13 6 Homo sapiens Human POU domain class 5 transcription factor 1 like protein 1 Octamer binding protein 3 like Homo sapiens Human POU domain class 5 transcription factor 1 like protein 1 Octamer binding protein 3 like Homo sapiens Human Late cornified envelope protein 3C Late envelope protein 15 Small proline rich like epidermal differentiation complex protein 3A Homo sapiens Human Late cornified envelope protein 3C Late envelope protein 15 Small proline rich like epidermal differentiation complex protein 3A Homo sapiens Human Late cornified envelope protein 3C Late envelope protein 15 Small proline rich like epidermal differentiation complex protein 3A Homo sapiens Human Arginine-glutamic acid dipeptide repeats protein Atrophin 1 like protein Atrophin 1 related protein Homo sapiens Human Cadherin-like protein 26 precursor Cadherin like protein VR20 Homo sapiens Human Cadherin-like protein 26 precursor Cadherin like protein VR20 Homo sapiens Human Regenerating islet derived protein 4 precursor Reg IV REG like protein Gastrointestinal secretory protein Homo sapiens Human Zinc finger protein 691 Homo sapiens Human Protein yippee like 4 Homo sapiens Human Regenerating islet derived protein 4 precursor Reg IV REG like protein Gastrointestinal secretory protein Homo sapiens Human Regenerating islet derived protein 4 precursor Reg IV REG like protein Gastrointestinal secretory protein Homo sapiens Human Regenerating islet derived protein 4 precursor Reg IV REG like protein Gastrointestinal secretory protein Homo sapiens Human Regenerating islet derived protein 4 precursor Reg IV REG like protein Gastrointestinal secretory protein Homo sapiens Human Major prion protein precursor PrP PrP27 30 PrP33 35C ASCR CD230 antigen Homo sapiens Human Major prion protein precursor PrP PrP27 30 PrP33 35C ASCR CD230 antigen Homo sapiens Human 4 764 764 364 364 455 455 826 874 874 298 298 298 474 520 520 444 624 413 689 689 312 312 515 515 148 1 506 2 2.10 507 508 2.09 2.08 509 2.07 510 2.05 511 2.05 512 2.05 513 514 515 2.04 2.04 2.03 516 2.01 517 2.01 518 2.01 519 2.01 520 2.01 521 2.00 522 1.99 523 1.99 524 1.99 525 1.96 526 527 528 529 530 531 1.95 1.95 1.92 1.91 1.91 1.90 532 1.88 3 Major prion protein precursor PrP PrP27 30 PrP33 35C ASCR CD230 antigen Homo sapiens Human Transmembrane protein 106B Homo sapiens Human PHD finger protein 21A BRAF35 HDAC complex protein BHC80 BHC80a Homo sapiens Human Actin-binding Rho activating protein Striated muscle activator of Rho dependent signaling STARS Homo sapiens Human Regenerating islet derived protein 4 precursor Reg IV REG like protein Gastrointestinal secretory protein Homo sapiens Human Regenerating islet derived protein 4 precursor Reg IV REG like protein Gastrointestinal secretory protein Homo sapiens Human Regenerating islet derived protein 4 precursor Reg IV REG like protein Gastrointestinal secretory protein Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human Ly6/PLAUR domain containing protein 3 precursor GPI anchored metastasis associated protein C4 4A homolog Matrigel induced gene C4 protein MIG C4 Homo sapiens Human Olfactory receptor 10A7 Olfactory receptor OR12 6 Homo sapiens Human Olfactory receptor 10A7 Olfactory receptor OR12 6 Homo sapiens Human Olfactory receptor 10A7 Olfactory receptor OR12 6 Homo sapiens Human Olfactory receptor 10A7 Olfactory receptor OR12 6 Homo sapiens Human Olfactory receptor 10A7 Olfactory receptor OR12 6 Homo sapiens Human Uncharacterized protein C10orf38 precursor Astroprincin Homo sapiens Human Protein transport protein Sec24D SEC24 related protein D Homo sapiens Human Protein transport protein Sec24D SEC24 related protein D Homo sapiens Human Protein transport protein Sec24D SEC24 related protein D Homo sapiens Human Complex I intermediate associated protein 30 mitochondrial precursor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly factor 1 Homo sapiens Human Protein yippee like 4 Homo sapiens Human Protein yippee like 4 Homo sapiens Human Cathepsin S precursor EC 3 4 22 27 Homo sapiens Human Zinc finger protein 225 Homo sapiens Human Zinc finger protein 225 Homo sapiens Human Zinc finger protein 250 Zinc finger protein 647 Homo sapiens Human Complex I intermediate associated protein 30 mitochondrial precursor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly factor 1 Homo sapiens Human 4 515 955 729 506 341 341 341 978 978 903 242 242 242 242 242 667 443 443 443 456 448 448 445 430 430 584 422 149 1 533 2 1.88 534 535 1.87 1.85 536 1.83 537 1.83 538 1.81 539 1.81 540 1.80 541 1.80 542 1.79 543 1.78 544 1.77 545 1.71 546 1.71 547 1.70 548 1.70 549 1.69 550 1.67 551 1.63 552 1.61 553 1.60 554 1.60 555 1.58 556 1.58 3 4 Complex I intermediate associated protein 30 mitochondrial precur422 sor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly factor 1 Homo sapiens Human Protein ARMCX6 Homo sapiens Human 560 Glia-activating factor precursor GAF Fibroblast growth factor 9 FGF 941 9 HBGF 9 Homo sapiens Human Olfactory receptor 10A7 Olfactory receptor OR12 6 Homo sapiens 680 Human Olfactory receptor 10A7 Olfactory receptor OR12 6 Homo sapiens 680 Human Complex I intermediate associated protein 30 mitochondrial precur249 sor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly factor 1 Homo sapiens Human Complex I intermediate associated protein 30 mitochondrial precur249 sor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly factor 1 Homo sapiens Human Arginine-glutamic acid dipeptide repeats protein Atrophin 1 like 461 protein Atrophin 1 related protein Homo sapiens Human Arginine-glutamic acid dipeptide repeats protein Atrophin 1 like 461 protein Atrophin 1 related protein Homo sapiens Human Olfactory receptor 10A7 Olfactory receptor OR12 6 Homo sapiens 996 Human Arginine-glutamic acid dipeptide repeats protein Atrophin 1 like 719 protein Atrophin 1 related protein Homo sapiens Human Glycine cleavage system H protein mitochondrial precursor Homo 850 sapiens Human Regenerating islet derived protein 4 precursor Reg IV REG like 663 protein Gastrointestinal secretory protein Homo sapiens Human Regenerating islet derived protein 4 precursor Reg IV REG like 663 protein Gastrointestinal secretory protein Homo sapiens Human Replication protein A 14 kDa subunit RP A RF A Replication factor 255 A protein 3 p14 Homo sapiens Human Replication protein A 14 kDa subunit RP A RF A Replication factor 255 A protein 3 p14 Homo sapiens Human Arginine-glutamic acid dipeptide repeats protein Atrophin 1 like 716 protein Atrophin 1 related protein Homo sapiens Human Epididymal-specific lipocalin 9 precursor MUP like lipocalin Homo 804 sapiens Human Homeobox protein OTX2 Orthodenticle homolog 2 Homo sapiens 798 Human Regenerating islet derived protein 4 precursor Reg IV REG like 1009 protein Gastrointestinal secretory protein Homo sapiens Human Arginine-glutamic acid dipeptide repeats protein Atrophin 1 like 577 protein Atrophin 1 related protein Homo sapiens Human Arginine-glutamic acid dipeptide repeats protein Atrophin 1 like 577 protein Atrophin 1 related protein Homo sapiens Human Regenerating islet derived protein 4 precursor Reg IV REG like 262 protein Gastrointestinal secretory protein Homo sapiens Human Regenerating islet derived protein 4 precursor Reg IV REG like 262 protein Gastrointestinal secretory protein Homo sapiens Human 150 1 557 558 559 560 561 562 563 2 1.56 1.56 1.56 1.55 1.55 1.55 1.53 564 1.52 565 1.52 566 1.51 567 1.51 568 1.50 569 1.50 570 571 572 1.48 1.48 1.47 573 1.47 574 1.46 575 1.46 576 1.45 577 1.45 578 579 580 581 582 1.44 1.44 1.43 1.43 1.41 583 1.40 584 1.39 3 Arylsulfatase J precursor EC 3 1 6 ASJ Homo sapiens Human Arylsulfatase J precursor EC 3 1 6 ASJ Homo sapiens Human Arylsulfatase J precursor EC 3 1 6 ASJ Homo sapiens Human Protein yippee like 4 Homo sapiens Human Protein yippee like 4 Homo sapiens Human Protein yippee like 4 Homo sapiens Human L-lactate dehydrogenase B chain EC 1 1 1 27 LDH B LDH heart subunit LDH H Renal carcinoma antigen NY REN 46 Homo sapiens Human Complex I intermediate associated protein 30 mitochondrial precursor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly factor 1 Homo sapiens Human Complex I intermediate associated protein 30 mitochondrial precursor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly factor 1 Homo sapiens Human HLA class II histocompatibility antigen DM beta chain precursor MHC class II antigen DMB Homo sapiens Human HLA class II histocompatibility antigen DM beta chain precursor MHC class II antigen DMB Homo sapiens Human Nuclear pore complex protein Nup153 Nucleoporin Nup153 153 kDa nucleoporin Homo sapiens Human Nuclear pore complex protein Nup153 Nucleoporin Nup153 153 kDa nucleoporin Homo sapiens Human Putative uncharacterized protein C10orf130 Homo sapiens Human Putative uncharacterized protein C10orf130 Homo sapiens Human Kv channel interacting protein 1 KChIP1 A type potassium channel modulatory protein 1 Potassium channel interacting protein 1 Vesicle APC binding protein Homo sapiens Human Kv channel interacting protein 1 KChIP1 A type potassium channel modulatory protein 1 Potassium channel interacting protein 1 Vesicle APC binding protein Homo sapiens Human Olfactory receptor 2H1 Olfactory receptor OR6 32 Hs6M1 16 Olfactory receptor 6 2 OR6 2 OLFR42A 9004 14 9026 2 Homo sapiens Human Olfactory receptor 2H1 Olfactory receptor OR6 32 Hs6M1 16 Olfactory receptor 6 2 OR6 2 OLFR42A 9004 14 9026 2 Homo sapiens Human Arginine-glutamic acid dipeptide repeats protein Atrophin 1 like protein Atrophin 1 related protein Homo sapiens Human Arginine-glutamic acid dipeptide repeats protein Atrophin 1 like protein Atrophin 1 related protein Homo sapiens Human Protein yippee like 4 Homo sapiens Human Protein yippee like 4 Homo sapiens Human Protein yippee like 4 Homo sapiens Human Protein yippee like 4 Homo sapiens Human Phosducin PHD 33 kDa phototransducing protein MEKA protein Homo sapiens Human Zinc finger HIT domain containing protein 1 Cyclin G1 binding protein 1 Homo sapiens Human Zinc finger CCHC type and RNA binding motif containing protein 1 U11 U12 snRNP 31 kDa protein U11 U12 31K Homo sapiens Human 4 161 161 161 369 369 369 643 477 477 510 510 503 503 358 358 856 856 854 854 576 576 554 554 702 702 845 879 921 151 1 585 586 587 588 2 1.37 1.37 1.37 1.36 589 1.35 590 1.35 591 1.34 592 1.34 593 1.33 594 1.33 595 1.33 596 597 1.30 1.29 598 1.29 599 1.29 600 1.26 601 1.26 602 1.24 603 1.22 604 605 1.22 1.21 606 607 608 609 1.20 1.20 1.20 1.19 610 1.17 611 1.17 3 Bcl-2-modifying factor Homo sapiens Human Bcl-2-modifying factor Homo sapiens Human Bcl-2-modifying factor Homo sapiens Human Chondroitin sulfate glucuronyltransferase EC 2 4 1 226 N acetylgalactosaminyl proteoglycan 3 beta glucuronosyltransferase Chondroitin glucuronyltransferase II CSGlcA T Homo sapiens Human Cadherin-like protein 26 precursor Cadherin like protein VR20 Homo sapiens Human Cadherin-like protein 26 precursor Cadherin like protein VR20 Homo sapiens Human Nuclear pore complex protein Nup153 Nucleoporin Nup153 153 kDa nucleoporin Homo sapiens Human Nuclear pore complex protein Nup153 Nucleoporin Nup153 153 kDa nucleoporin Homo sapiens Human Nuclear pore complex protein Nup153 Nucleoporin Nup153 153 kDa nucleoporin Homo sapiens Human Nuclear pore complex protein Nup153 Nucleoporin Nup153 153 kDa nucleoporin Homo sapiens Human Nuclear pore complex protein Nup153 Nucleoporin Nup153 153 kDa nucleoporin Homo sapiens Human Uncharacterized protein C2orf21 Homo sapiens Human Zinc finger protein 295 Zinc finger and BTB domain containing protein 21 Homo sapiens Human Zinc finger protein 295 Zinc finger and BTB domain containing protein 21 Homo sapiens Human Zinc finger protein 295 Zinc finger and BTB domain containing protein 21 Homo sapiens Human Keratin, type I cytoskeletal 9 Cytokeratin 9 CK 9 Keratin 9 K9 Homo sapiens Human Keratin, type I cytoskeletal 9 Cytokeratin 9 CK 9 Keratin 9 K9 Homo sapiens Human Olfactory receptor 10A7 Olfactory receptor OR12 6 Homo sapiens Human Olfactory receptor 10A7 Olfactory receptor OR12 6 Homo sapiens Human Olfactory receptor 10A7 Olfactory receptor OR12 6 Homo sapiens Human Glycine cleavage system H protein mitochondrial precursor Homo sapiens Human Putative uncharacterized protein C10orf130 Homo sapiens Human Putative uncharacterized protein C10orf130 Homo sapiens Human Putative uncharacterized protein C10orf130 Homo sapiens Human Inositol-pentakisphosphate 2 kinase EC 2 7 1 158 Inositol 1 3 4 5 6 pentakisphosphate 2 kinase Ins 1 3 4 5 6 P5 2 kinase InsP5 2 kinase IPK1 homolog Homo sapiens Human Complex I intermediate associated protein 30 mitochondrial precursor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly factor 1 Homo sapiens Human Complex I intermediate associated protein 30 mitochondrial precursor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly factor 1 Homo sapiens Human 4 383 383 383 605 349 349 496 496 493 493 493 471 454 454 454 524 524 551 674 674 819 357 357 357 928 333 333 152 1 612 2 1.17 613 1.17 614 1.17 615 616 617 1.15 1.15 1.14 618 1.13 619 1.12 620 1.12 621 1.11 622 1.11 623 1.11 624 1.11 625 1.09 626 627 628 629 630 1.08 1.07 1.07 1.07 1.06 631 1.05 632 1.05 633 1.04 634 1.03 635 1.03 3 Complex I intermediate associated protein 30 mitochondrial precursor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly factor 1 Homo sapiens Human Complex I intermediate associated protein 30 mitochondrial precursor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly factor 1 Homo sapiens Human Complex I intermediate associated protein 30 mitochondrial precursor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly factor 1 Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human Vacuolar protein sorting associated protein 25 hVps25 ELL associated protein of 20 kDa Dermal papilla derived protein 9 Homo sapiens Human Chromaffin granule amine transporter Vesicular amine transporter 1 VAT1 Solute carrier family 18 member 1 Homo sapiens Human Cytochrome c oxidase polypeptide 8 isoform 3 mitochondrial precursor EC 1 9 3 1 Cytochrome c oxidase polypeptide VIII isoform 3 Cytochrome c oxidase subunit 8 3 COX VIII 3 Homo sapiens Human Cytochrome c oxidase polypeptide 8 isoform 3 mitochondrial precursor EC 1 9 3 1 Cytochrome c oxidase polypeptide VIII isoform 3 Cytochrome c oxidase subunit 8 3 COX VIII 3 Homo sapiens Human Glutaryl-CoA dehydrogenase mitochondrial precursor EC 1 3 99 7 GCD Homo sapiens Human Glutaryl-CoA dehydrogenase mitochondrial precursor EC 1 3 99 7 GCD Homo sapiens Human Glutaryl-CoA dehydrogenase mitochondrial precursor EC 1 3 99 7 GCD Homo sapiens Human Glutaryl-CoA dehydrogenase mitochondrial precursor EC 1 3 99 7 GCD Homo sapiens Human Brix domain containing protein 2 Ribosome biogenesis protein Brix Homo sapiens Human Frizzled-2 precursor Fz 2 hFz2 FzE2 Homo sapiens Human Acyl-CoA-binding domain containing protein 7 Homo sapiens Human Acyl-CoA-binding domain containing protein 7 Homo sapiens Human Acyl-CoA-binding domain containing protein 7 Homo sapiens Human Probable U3 small nucleolar RNA associated protein 11 U3 snoRNA associated protein 11 UTP11 like protein Homo sapiens Human Rab GDP dissociation inhibitor alpha Rab GDI alpha Guanosine diphosphate dissociation inhibitor 1 GDI 1 XAP 4 Oligophrenin 2 Homo sapiens Human Rab GDP dissociation inhibitor alpha Rab GDI alpha Guanosine diphosphate dissociation inhibitor 1 GDI 1 XAP 4 Oligophrenin 2 Homo sapiens Human Regenerating islet derived protein 4 precursor Reg IV REG like protein Gastrointestinal secretory protein Homo sapiens Human Arginine-glutamic acid dipeptide repeats protein Atrophin 1 like protein Atrophin 1 related protein Homo sapiens Human Arginine-glutamic acid dipeptide repeats protein Atrophin 1 like protein Atrophin 1 related protein Homo sapiens Human 4 333 333 333 314 314 478 810 863 863 734 734 734 734 985 527 686 686 686 704 568 568 458 556 556 153 1 636 2 1.01 637 638 639 640 1.00 0.99 0.99 0.98 641 0.97 642 0.97 643 0.96 644 0.96 645 0.94 646 647 648 649 650 651 0.90 0.89 0.89 0.89 0.88 0.82 652 653 654 655 0.79 0.78 0.75 0.73 656 0.73 657 658 659 0.70 0.70 0.69 660 0.68 661 0.68 662 0.64 663 0.64 664 0.62 3 Vacuolar protein sorting associated protein 25 hVps25 ELL associated protein of 20 kDa Dermal papilla derived protein 9 Homo sapiens Human Uncharacterized protein C14orf112 precursor Homo sapiens Human Nucleolar protein 66 hsNO66 Homo sapiens Human Nucleolar protein 66 hsNO66 Homo sapiens Human Arginine-glutamic acid dipeptide repeats protein Atrophin 1 like protein Atrophin 1 related protein Homo sapiens Human Actin-binding Rho activating protein Striated muscle activator of Rho dependent signaling STARS Homo sapiens Human Actin-binding Rho activating protein Striated muscle activator of Rho dependent signaling STARS Homo sapiens Human 26S proteasome associated UCH37 interacting protein 1 X linked protein STS1769 Homo sapiens Human 26S proteasome associated UCH37 interacting protein 1 X linked protein STS1769 Homo sapiens Human 26S proteasome non ATPase regulatory subunit 14 26S proteasome regulatory subunit rpn11 26S proteasome associated PAD1 homolog 1 Homo sapiens Human Transmembrane protein 78 Homo sapiens Human REST corepressor 3 Homo sapiens Human REST corepressor 3 Homo sapiens Human REST corepressor 3 Homo sapiens Human Frizzled-2 precursor Fz 2 hFz2 FzE2 Homo sapiens Human Rho guanine nucleotide exchange factor 5 Guanine nucleotide regulatory protein TIM Oncogene TIM p60 TIM Transforming immortalized mammary oncogene Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human Coiled-coil domain containing protein 25 Homo sapiens Human Lysozyme-like protein 4 precursor Homo sapiens Human UNC93 homolog A UNC 93A protein HmUNC 93A Homo sapiens Human UNC93 homolog A UNC 93A protein HmUNC 93A Homo sapiens Human Protein mago nashi homolog Homo sapiens Human Protein mago nashi homolog Homo sapiens Human HLA class II histocompatibility antigen DM beta chain precursor MHC class II antigen DMB Homo sapiens Human CD302 antigen precursor C type lectin domain family 13 member A C type lectin BIMLEC Type I transmembrane C type lectin receptor DCL 1 Homo sapiens Human CD302 antigen precursor C type lectin domain family 13 member A C type lectin BIMLEC Type I transmembrane C type lectin receptor DCL 1 Homo sapiens Human Probable RNA binding protein 18 RNA binding motif protein 18 Homo sapiens Human Probable RNA binding protein 18 RNA binding motif protein 18 Homo sapiens Human Matrix metalloproteinase 19 precursor EC 3 4 24 MMP 19 Matrix metalloproteinase RASI MMP 18 Homo sapiens Human 4 475 822 481 481 721 501 501 837 837 774 861 441 441 441 539 596 972 876 462 792 792 668 668 511 799 799 785 785 981 154 1 665 666 667 668 2 0.60 0.58 0.58 0.55 669 0.54 670 0.53 671 0.53 672 0.53 673 674 675 0.52 0.51 0.50 676 0.49 677 678 0.46 0.41 679 0.41 680 681 0.37 0.36 3 Protein yippee like 4 Homo sapiens Human Leucine-rich repeat containing protein 51 Homo sapiens Human Leucine-rich repeat containing protein 51 Homo sapiens Human HLA class II histocompatibility antigen DM beta chain precursor MHC class II antigen DMB Homo sapiens Human GTP-binding protein Di Ras1 Distinct subgroup of the Ras family member 1 Ras related inhibitor of cell growth Rig protein Small GTP binding tumor suppressor 1 Homo sapiens Human Taste receptor type 2 member 42 T2R42 T2R55 Homo sapiens Human Taste receptor type 2 member 42 T2R42 T2R55 Homo sapiens Human Taste receptor type 2 member 42 T2R42 T2R55 Homo sapiens Human Uncharacterized protein C21orf59Homo sapiens Human Uncharacterized protein C16orf53 Homo sapiens Human Immunoglobulin superfamily member 8 precursor CD81 partner 3 Glu Trp Ile EWI motif containing protein 2 EWI 2 Keratinocytes associated transmembrane protein 4 KCT 4 LIR D1 CD316 antigen Homo sapiens Human B-lymphocyte antigen CD19 precursor Differentiation antigen CD19 B lymphocyte surface antigen B4 Leu 12 Homo sapiens Human Uncharacterized protein C20orf197 Homo sapiens Human Cysteine-rich protein 3 CRP3 Chromosome 6 LIM domain only protein h6LIMo Homo sapiens Human Cysteine-rich protein 3 CRP3 Chromosome 6 LIM domain only protein h6LIMo Homo sapiens Human Putative RNA methylase C6orf75 EC 2 1 1 Homo sapiens Human Apolipoprotein F precursor Apo F Lipid transfer inhibitor protein LTIP Homo sapiens Human 4 694 775 775 500 772 803 803 803 894 549 502 852 860 793 793 823 802 155 Ɍɚɛɥɢɰɚ 2 ȼɟɪɨɹɬɧɨɫɬɶ ʋ ɩ/ɩ ɫɨɜɩɚɞɟɧɢɹ (%) 1 2 1 2 100.00 76.56 3 47.89 4 5 38.11 34.16 6 7 32.98 31.08 8 9 10 11 27.09 17.54 15.46 15.37 12 15.07 13 14.41 14 15 16 14.15 14.03 13.59 17 13.44 18 13.38 19 20 12.58 12.49 21 12.03 22 23 24 25 11.65 11.59 11.54 11.50 ID ɛɟɥɤɨɜ ɞɥɹ CD34+ȽɋɄ (1-ɹ ɮɪɚɤɰɢɹ, 2-ɹ ɩɨɜɬɨɪɧɨɫɬɶ) ɇɨɦɟɪ ɩɹɬɧɚ 3 4 HEAT repeat containing protein 2 Homo sapiens Human Zinc finger and BTB domain containing protein 41 Homo sapiens Human Zinc finger protein 250 Zinc finger protein 647 Homo sapiens Human Toll-like receptor 8 precursor CD288 antigen Homo sapiens Human Hemoglobin subunit beta Hemoglobin beta chain Beta globin Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human Zinc finger protein 250 Zinc finger protein 647 Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human Zinc finger protein 250 Zinc finger protein 647 Homo sapiens Human Complex I intermediate associated protein 30 mitochondrial precursor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly factor 1 Homo sapiens Human Arginine-glutamic acid dipeptide repeats protein Atrophin 1 like protein Atrophin 1 related protein Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human Rho guanine nucleotide exchange factor 5 Guanine nucleotide regulatory protein TIM Oncogene TIM p60 TIM Transforming immortalized mammary oncogene Homo sapiens Human Hemoglobin subunit gamma 1 Hemoglobin gamma 1 chain Gamma 1 globin Hemoglobin gamma A chain Hb F Agamma Homo sapiens Human Metalloproteinase inhibitor 2 precursor TIMP 2 Tissue inhibitor of metalloproteinases 2 CSC 21K Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human Cathepsin L2 precursor EC 3 4 22 43 Cathepsin V Cathepsin U Homo sapiens Human Complex I intermediate associated protein 30 mitochondrial precursor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly factor 1 Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human Transmembrane protein 106B Homo sapiens Human 973 1497 1185 994 895 691 467 1487 1102 376 1212 1389 373 1402 1158 1457 1276 828 655 1016 252 1083 1132 426 1249 156 1 2 3 4 26 27 28 29 30 31 32 33 34 35 36 37 10.87 10.80 10.75 10.10 10.07 10.03 9.94 9.92 9.77 9.44 9.21 9.15 351 1046 1476 1070 1015 334 1183 548 1078 419 1520 1482 38 39 40 41 42 43 44 9.03 8.92 8.84 8.84 8.72 8.58 8.54 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 7.97 7.87 7.84 7.84 7.82 7.80 7.71 7.66 7.66 7.57 7.55 7.50 7.44 7.37 7.25 7.17 7.07 7.07 6.99 6.97 65 6.97 Keratin-associated protein 21 2 Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human Bcl-2-modifying factor Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human Complement component C8 alpha chain precursor Complement component 8 subunit alpha Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human Calcium/calmodulin-dependent protein kinase kinase 1 EC 2 7 11 17 Calcium calmodulin dependent protein kinase kinase alpha CaM kinase kinase alpha CaM KK alpha CaMKK alpha CaMKK 1 CaM kinase IV kinase Homo sapiens Human Transmembrane protein 106B Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human Transmembrane protein 106B Homo sapiens Human Transmembrane protein 106B Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human Zinc finger protein 225 Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human Olfactory receptor 10A7 Olfactory receptor OR12 6 Homo sapiens Human Olfactory receptor 10A7 Olfactory receptor OR12 6 Homo sapiens Human 479 1310 377 377 1035 1145 1395 1062 647 1163 1163 1379 1114 763 428 428 1157 1019 352 805 1147 627 267 718 718 372 1136 1136 157 1 2 3 4 66 67 68 6.83 6.79 6.64 1079 1044 1366 69 70 6.53 6.44 71 72 73 74 6.40 6.30 6.21 6.20 75 6.18 76 77 6.16 6.12 78 6.04 79 6.03 80 81 82 5.92 5.91 5.86 83 5.85 84 5.81 85 5.71 86 5.64 87 88 89 90 5.58 5.55 5.55 5.52 91 5.50 Keratin-associated protein 21 2 Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human Olfactory receptor 10A7 Olfactory receptor OR12 6 Homo sapiens Human Transmembrane protein 106B Homo sapiens Human Complex I intermediate associated protein 30 mitochondrial precursor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly factor 1 Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human Transmembrane protein 106B Homo sapiens Human Hemoglobin subunit gamma 1 Hemoglobin gamma 1 chain Gamma 1 globin Hemoglobin gamma A chain Hb F Agamma Homo sapiens Human Zinc finger protein 250 Zinc finger protein 647 Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human Olfactory receptor 10A7 Olfactory receptor OR12 6 Homo sapiens Human Complex I intermediate associated protein 30 mitochondrial precursor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly factor 1 Homo sapiens Human Ladinin 1 Lad 1 120 kDa linear IgA bullous dermatosis antigen 97 kDa linear IgA bullous dermatosis antigen Linear IgA disease antigen homolog LadA Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human Transmembrane protein 106B Homo sapiens Human Short palate lung and nasal epithelium carcinoma associated protein 2 precursor Parotid secretory protein PSP Homo sapiens Human T-cell leukemia translocation associated gene protein Homo sapiens Human Arginine-glutamic acid dipeptide repeats protein Atrophin 1 like protein Atrophin 1 related protein Homo sapiens Human WAP four disulfide core domain protein 1 precursor Prostate stromal protein ps20 ps20 growth inhibitor Homo sapiens Human Complex I intermediate associated protein 30 mitochondrial precursor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly factor 1 Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human Olfactory receptor 10A7 Olfactory receptor OR12 6 Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human 1173 578 466 1116 531 1272 1196 1126 1278 187 504 523 1392 702 1112 378 1398 614 1060 1106 1106 481 1337 158 1 2 3 4 92 93 94 95 96 5.45 5.43 5.41 5.37 5.33 618 1156 1608 329 1087 97 5.30 98 5.24 99 5.24 100 5.23 101 102 103 104 105 106 107 108 5.21 5.20 5.18 5.18 5.16 5.16 5.12 5.09 109 5.08 110 5.08 111 112 5.05 4.94 113 114 4.87 4.86 115 116 117 118 119 120 121 122 123 124 4.83 4.77 4.73 4.70 4.67 4.67 4.63 4.61 4.59 4.51 Keratin-associated protein 21 2 Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human Olfactory receptor 10A7 Olfactory receptor OR12 6 Homo sapiens Human Zinc finger protein 250 Zinc finger protein 647 Homo sapiens Human Complex I intermediate associated protein 30 mitochondrial precursor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly factor 1 Homo sapiens Human Complex I intermediate associated protein 30 mitochondrial precursor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly factor 1 Homo sapiens Human Olfactory receptor 10A7 Olfactory receptor OR12 6 Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human REST corepressor 3 Homo sapiens Human Olfactory receptor 10A7 Olfactory receptor OR12 6 Homo sapiens Human Zinc finger and BTB domain containing protein 41 Homo sapiens Human Zinc finger and BTB domain containing protein 41 Homo sapiens Human E3 WAP four disulfide core domain protein 1 precursor Prostate stromal protein ps20 ps20 growth inhibitor Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human Arginine-glutamic acid dipeptide repeats protein Atrophin 1 like protein Atrophin 1 related protein Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human Transmembrane protein 106B Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human 1400 1007 1007 1160 1168 669 1036 1036 1013 1013 1201 1352 1089 1089 1071 1282 1138 602 721 766 315 1148 1003 1003 1376 1105 429 1135 159 1 2 3 4 125 4.50 1023 126 127 128 4.44 4.43 4.41 129 4.41 130 4.36 131 4.33 132 133 134 135 136 137 4.31 4.31 4.30 4.29 4.27 4.23 138 139 140 141 4.22 4.22 4.22 4.19 142 143 144 145 4.17 4.16 4.15 4.14 146 147 4.07 4.03 148 3.99 149 150 151 152 3.98 3.98 3.93 3.89 153 154 3.88 3.87 Complex I intermediate associated protein 30 mitochondrial precursor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly factor 1 Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human G-protein-signaling modulator 1 Activator of G protein signaling 3 Homo sapiens Human G-protein-signaling modulator 1 Activator of G protein signaling 3 Homo sapiens Human Complex I intermediate associated protein 30 mitochondrial precursor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly factor 1 Homo sapiens Human Late cornified envelope protein 3C Late envelope protein 15 Small proline rich like epidermal differentiation complex protein 3A Homo sapiens Human SOX-12 protein SOX 22 protein Homo sapiens Human SOX-12 protein SOX 22 protein Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human Arginine-glutamic acid dipeptide repeats protein Atrophin 1 like protein Atrophin 1 related protein Homo sapiens Human Taste receptor type 2 member 4 T2R4 Homo sapiens Human Taste receptor type 2 member 4 T2R4 Homo sapiens Human Taste receptor type 2 member 4 T2R4 Homo sapiens Human Olfactory receptor 10A7 Olfactory receptor OR12 6 Homo sapiens Human Cullin-4B CUL 4B Homo sapiens Human Cathepsin E precursor EC 3 4 23 34 Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human Ly6/PLAUR domain containing protein 3 precursor GPI anchored metastasis associated protein C4 4A homolog Matrigel induced gene C4 protein MIG C4 Homo sapiens Human Cullin-4B CUL 4B Homo sapiens Human Growth/differentiation factor 7 precursor GDF 7 Homo sapiens Human Trefoil factor 3 precursor Intestinal trefoil factor hP1 B Homo sapiens Human Actin, cytoplasmic 2 Gamma actin Homo sapiens Human Actin, cytoplasmic 2 Gamma actin Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human Complex I intermediate associated protein 30 mitochondrial precursor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly factor 1 Homo sapiens Human Zinc finger protein 225 Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human 521 760 582 582 810 754 664 664 635 1109 775 1184 826 826 826 725 738 815 743 546 704 822 225 938 938 505 1014 1188 497 160 1 2 3 4 155 3.86 791 156 3.86 157 3.86 158 159 160 161 162 3.84 3.84 3.84 3.84 3.83 163 3.83 164 3.82 165 3.81 166 3.81 167 3.80 168 169 170 171 172 3.79 3.78 3.77 3.77 3.73 173 3.66 174 3.66 175 176 3.65 3.60 177 3.59 178 3.58 Complex I intermediate associated protein 30 mitochondrial precursor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly factor 1 Homo sapiens Human Complex I intermediate associated protein 30 mitochondrial precursor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly factor 1 Homo sapiens Human Complex I intermediate associated protein 30 mitochondrial precursor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly factor 1 Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human Regenerating islet derived protein 4 precursor Reg IV REG like protein Gastrointestinal secretory protein Homo sapiens Human Regenerating islet derived protein 4 precursor Reg IV REG like protein Gastrointestinal secretory protein Homo sapiens Human Complex I intermediate associated protein 30 mitochondrial precursor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly factor 1 Homo sapiens Human Complex I intermediate associated protein 30 mitochondrial precursor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly factor 1 Homo sapiens Human Complex I intermediate associated protein 30 mitochondrial precursor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly factor 1 Homo sapiens Human Complex I intermediate associated protein 30 mitochondrial precursor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly factor 1 Homo sapiens Human Taste receptor type 2 member 4 T2R4 Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human Regenerating islet derived protein 4 precursor Reg IV REG like protein Gastrointestinal secretory protein Homo sapiens Human Regenerating islet derived protein 4 precursor Reg IV REG like protein Gastrointestinal secretory protein Homo sapiens Human Regenerating islet derived protein 4 precursor Reg IV REG like protein Gastrointestinal secretory protein Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human Cadherin-like protein 26 precursor Cadherin like protein VR20 Homo sapiens Human Kinesin-like protein KIF3A Microtubule plus end directed kinesin motor 3A Homo sapiens Human Complex I intermediate associated protein 30 mitochondrial precursor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly factor 1 Homo sapiens Human 791 791 321 321 321 321 543 543 507 807 807 1194 992 1081 355 355 486 755 755 1498 1429 1367 514 161 1 2 3 4 179 3.57 601 180 181 182 183 184 185 186 3.56 3.56 3.55 3.54 3.54 3.54 3.52 187 3.49 188 3.45 189 3.44 190 3.44 191 3.39 192 3.39 193 194 195 196 3.38 3.36 3.36 3.33 197 198 3.32 3.29 199 3.29 200 201 202 3.28 3.28 3.27 203 3.26 204 3.24 Complex I intermediate associated protein 30 mitochondrial precursor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly factor 1 Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human Transmembrane protein 106B Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human Complex I intermediate associated protein 30 mitochondrial precursor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly factor 1 Homo sapiens Human Complex I intermediate associated protein 30 mitochondrial precursor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly factor 1 Homo sapiens Human Complex I intermediate associated protein 30 mitochondrial precursor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly factor 1 Homo sapiens Human Integrin-linked protein kinase EC 2 7 11 1 ILK 1 ILK 2 59 kDa serine threonine protein kinase p59ILK Homo sapiens Human Integrin-linked protein kinase EC 2 7 11 1 ILK 1 ILK 2 59 kDa serine threonine protein kinase p59ILK Homo sapiens Human Regenerating islet derived protein 4 precursor Reg IV REG like protein Gastrointestinal secretory protein Homo sapiens Human Regenerating islet derived protein 4 precursor Reg IV REG like protein Gastrointestinal secretory protein Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human Olfactory receptor 10A7 Olfactory receptor OR12 6 Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human Olfactory receptor 10A7 Olfactory receptor OR12 6 Homo sapiens Human Olfactory receptor 10A7 Olfactory receptor OR12 6 Homo sapiens Human Zinc finger protein 225 Homo sapiens Human Zinc finger protein 225 Homo sapiens Human Complex I intermediate associated protein 30 mitochondrial precursor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly factor 1 Homo sapiens Human Late cornified envelope protein 3C Late envelope protein 15 Small proline rich like epidermal differentiation complex protein 3A Homo sapiens Human Complex I intermediate associated protein 30 mitochondrial precursor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly factor 1 Homo sapiens Human 650 650 1299 415 415 415 1432 1217 552 797 797 519 519 488 787 787 804 1027 1012 1012 462 462 1403 1248 513 162 1 2 3 4 205 3.22 1100 206 3.20 207 3.18 208 3.18 209 3.16 210 211 3.10 3.09 212 3.08 213 3.08 214 215 216 3.07 3.07 3.06 217 3.03 218 219 220 3.01 2.99 2.96 221 222 2.94 2.92 223 2.90 224 2.90 225 226 227 228 2.89 2.88 2.85 2.84 Protein S100 A13 S100 calcium binding protein A13 Homo sapiens Human Regenerating islet derived protein 4 precursor Reg IV REG like protein Gastrointestinal secretory protein Homo sapiens Human Sororin Cell division cycle associated protein 5 p35 Homo sapiens Human Sororin Cell division cycle associated protein 5 p35 Homo sapiens Human Late cornified envelope protein 3C Late envelope protein 15 Small proline rich like epidermal differentiation complex protein 3A Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human Cadherin-like protein 26 precursor Cadherin like protein VR20 Homo sapiens Human B-lymphocyte antigen CD19 precursor Differentiation antigen CD19 B lymphocyte surface antigen B4 Leu 12 Homo sapiens Human B-lymphocyte antigen CD19 precursor Differentiation antigen CD19 B lymphocyte surface antigen B4 Leu 12 Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human Complex I intermediate associated protein 30 mitochondrial precursor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly factor 1 Homo sapiens Human Complex I intermediate associated protein 30 mitochondrial precursor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly factor 1 Homo sapiens Human Uncharacterized protein C1orf210 Homo sapiens Human Transmembrane protein 9B precursor Homo sapiens Human Zinc finger and BTB domain containing protein 41 Homo sapiens Human Component of gems 4 Gemin 4 p97 Homo sapiens Human Complex I intermediate associated protein 30 mitochondrial precursor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly factor 1 Homo sapiens Human Serpin A12 precursor Visceral adipose specific serpin Visceral adipose tissue derived serine protease inhibitor Vaspin OL 64 Homo sapiens Human Serpin A12 precursor Visceral adipose specific serpin Visceral adipose tissue derived serine protease inhibitor Vaspin OL 64 Homo sapiens Human Cathepsin E precursor EC 3 4 23 34 Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human 452 1077 1077 1242 389 527 856 856 757 757 802 499 698 1370 625 1252 789 941 941 873 1486 541 1161 163 1 2 3 4 229 230 231 232 2.84 2.83 2.77 2.75 1161 817 657 1263 233 234 235 236 2.74 2.74 2.74 2.70 237 2.70 238 2.70 239 240 2.66 2.65 241 2.64 242 2.64 243 2.64 244 245 2.59 2.58 246 2.57 247 2.57 248 2.55 249 2.52 250 2.51 251 2.49 252 2.49 Keratin-associated protein 21 2 Homo sapiens Human Melanocortin receptor 4 MC4 R Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human Olfactory receptor 10A7 Olfactory receptor OR12 6 Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human Arginine-glutamic acid dipeptide repeats protein Atrophin 1 like protein Atrophin 1 related protein Homo sapiens Human Arginine-glutamic acid dipeptide repeats protein Atrophin 1 like protein Atrophin 1 related protein Homo sapiens Human Arginine-glutamic acid dipeptide repeats protein Atrophin 1 like protein Atrophin 1 related protein Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human Trefoil factor 3 precursor Intestinal trefoil factor hP1 B Homo sapiens Human Complex I intermediate associated protein 30 mitochondrial precursor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly factor 1 Homo sapiens Human Complex I intermediate associated protein 30 mitochondrial precursor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly factor 1 Homo sapiens Human Complex I intermediate associated protein 30 mitochondrial precursor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly factor 1 Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human Calcium/calmodulin-dependent protein kinase kinase 1 EC 2 7 11 17 Calcium calmodulin dependent protein kinase kinase alpha CaM kinase kinase alpha CaM KK alpha CaMKK alpha CaMKK 1 CaM kinase IV kinase Homo sapiens Human Regenerating islet derived protein 4 precursor Reg IV REG like protein Gastrointestinal secretory protein Homo sapiens Human Regenerating islet derived protein 4 precursor Reg IV REG like protein Gastrointestinal secretory protein Homo sapiens Human Complex I intermediate associated protein 30 mitochondrial precursor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly factor 1 Homo sapiens Human Prolargin precursor Proline arginine rich end leucine rich repeat protein Homo sapiens Human Late cornified envelope protein 3C Late envelope protein 15 Small proline rich like epidermal differentiation complex protein 3A Homo sapiens Human Trefoil factor 3 precursor Intestinal trefoil factor hP1 B Homo sapiens Human Trefoil factor 3 precursor Intestinal trefoil factor hP1 B Homo sapiens Human 501 501 501 597 597 597 1049 645 534 534 534 1410 1259 800 800 232 604 692 772 772 164 1 2 3 4 253 254 255 256 257 2.47 2.47 2.47 2.44 2.43 948 948 948 1339 453 258 2.43 259 2.42 260 2.41 261 2.41 262 263 264 2.38 2.35 2.34 265 2.34 266 2.33 267 2.32 268 269 270 271 272 273 2.28 2.27 2.27 2.26 2.26 2.25 274 2.20 275 2.20 276 2.18 Asc-type amino acid transporter 1 Asc 1 Homo sapiens Human Asc-type amino acid transporter 1 Asc 1 Homo sapiens Human Asc-type amino acid transporter 1 Asc 1 Homo sapiens Human UPF0193 protein EVG1 Homo sapiens Human Trefoil factor 3 precursor Intestinal trefoil factor hP1 B Homo sapiens Human Trefoil factor 3 precursor Intestinal trefoil factor hP1 B Homo sapiens Human Complex I intermediate associated protein 30 mitochondrial precursor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly factor 1 Homo sapiens Human Regenerating islet derived protein 4 precursor Reg IV REG like protein Gastrointestinal secretory protein Homo sapiens Human Regenerating islet derived protein 4 precursor Reg IV REG like protein Gastrointestinal secretory protein Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human Complex I intermediate associated protein 30 mitochondrial precursor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly factor 1 Homo sapiens Human Complex I intermediate associated protein 30 mitochondrial precursor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly factor 1 Homo sapiens Human Calcium/calmodulin-dependent protein kinase kinase 1 EC 2 7 11 17 Calcium calmodulin dependent protein kinase kinase alpha CaM kinase kinase alpha CaM KK alpha CaMKK alpha CaMKK 1 CaM kinase IV kinase Homo sapiens Human Arginine-glutamic acid dipeptide repeats protein Atrophin 1 like protein Atrophin 1 related protein Homo sapiens Human Angiopoietin-1 precursor ANG 1 Homo sapiens Human Tenascin-N precursor TN N Homo sapiens Human Tenascin-N precursor TN N Homo sapiens Human Protein FAM23B Homo sapiens Human Protein FAM23B Homo sapiens Human Complex I intermediate associated protein 30 mitochondrial precursor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly factor 1 Homo sapiens Human Complex I intermediate associated protein 30 mitochondrial precursor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly factor 1 Homo sapiens Human Complex I intermediate associated protein 30 mitochondrial precursor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly factor 1 Homo sapiens Human Regenerating islet derived protein 4 precursor Reg IV REG like protein Gastrointestinal secretory protein Homo sapiens Human 453 549 330 330 1068 745 323 323 1031 605 806 1092 1092 653 653 574 540 540 811 165 1 2 3 4 277 2.18 811 278 279 280 281 2.17 2.17 2.15 2.14 282 2.11 283 2.11 284 2.11 285 2.10 286 2.10 287 2.10 288 2.09 289 2.09 290 291 292 293 2.07 2.07 2.06 2.05 294 2.05 295 296 2.04 2.03 297 2.03 298 299 2.02 2.01 Regenerating islet derived protein 4 precursor Reg IV REG like protein Gastrointestinal secretory protein Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human Olfactory receptor 10A7 Olfactory receptor OR12 6 Homo sapiens Human Regenerating islet derived protein 4 precursor Reg IV REG like protein Gastrointestinal secretory protein Homo sapiens Human Regenerating islet derived protein 4 precursor Reg IV REG like protein Gastrointestinal secretory protein Homo sapiens Human Regenerating islet derived protein 4 precursor Reg IV REG like protein Gastrointestinal secretory protein Homo sapiens Human Late cornified envelope protein 3C Late envelope protein 15 Small proline rich like epidermal differentiation complex protein 3A Homo sapiens Human Late cornified envelope protein 3C Late envelope protein 15 Small proline rich like epidermal differentiation complex protein 3A Homo sapiens Human Late cornified envelope protein 3C Late envelope protein 15 Small proline rich like epidermal differentiation complex protein 3A Homo sapiens Human Complex I intermediate associated protein 30 mitochondrial precursor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly factor 1 Homo sapiens Human Complex I intermediate associated protein 30 mitochondrial precursor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly factor 1 Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human Complex I intermediate associated protein 30 mitochondrial precursor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly factor 1 Homo sapiens Human Complex I intermediate associated protein 30 mitochondrial precursor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly factor 1 Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human Beta-defensin 131 precursor Defensin beta 131 Beta defensin 31 DEFB 31 Homo sapiens Human Beta-defensin 131 precursor Defensin beta 131 Beta defensin 31 DEFB 31 Homo sapiens Human Bcl-2-modifying factor Homo sapiens Human Trefoil factor 3 precursor Intestinal trefoil factor hP1 B Homo sapiens Human 458 458 649 1154 559 559 559 544 544 544 599 599 468 468 622 1190 1190 444 734 734 978 694 166 1 2 300 2.01 301 302 2.00 1.98 303 1.96 304 1.96 305 306 1.95 1.93 307 1.93 308 1.92 309 1.91 310 1.91 311 1.91 312 1.90 313 1.90 314 1.90 315 1.83 316 1.83 317 1.83 318 1.82 319 1.82 320 1.81 321 323 1.80 1.76 3 4 Trefoil factor 3 precursor Intestinal trefoil factor hP1 B Homo 694 sapiens Human Transmembrane protein 106B Homo sapiens Human 736 Segment polarity protein dishevelled homolog DVL 3 Dishe603 velled 3 DSH homolog 3 Homo sapiens Human Hepatocyte nuclear factor 6 HNF 6 One cut domain family 819 member 1 Homo sapiens Human Hepatocyte nuclear factor 6 HNF 6 One cut domain family 819 member 1 Homo sapiens Human UPF0184 protein C9orf16 EST00098 Homo sapiens Human 863 Olfactory receptor 10A7 Olfactory receptor OR12 6 Homo 611 sapiens Human Olfactory receptor 10A7 Olfactory receptor OR12 6 Homo 611 sapiens Human Arginine-glutamic acid dipeptide repeats protein Atrophin 1 like 545 protein Atrophin 1 related protein Homo sapiens Human Sorting nexin 18 Sorting nexin associated Golgi protein 1 SH3 705 and PX domain containing protein 3B Homo sapiens Human Sorting nexin 18 Sorting nexin associated Golgi protein 1 SH3 705 and PX domain containing protein 3B Homo sapiens Human Sorting nexin 18 Sorting nexin associated Golgi protein 1 SH3 705 and PX domain containing protein 3B Homo sapiens Human Cementoblastoma-derived protein 1 Cementum protein 23 CP 1073 23 Homo sapiens Human Cementoblastoma-derived protein 1 Cementum protein 23 CP 1073 23 Homo sapiens Human Cementoblastoma-derived protein 1 Cementum protein 23 CP 1073 23 Homo sapiens Human B-lymphocyte antigen CD19 precursor Differentiation antigen 685 CD19 B lymphocyte surface antigen B4 Leu 12 Homo sapiens Human B-lymphocyte antigen CD19 precursor Differentiation antigen 685 CD19 B lymphocyte surface antigen B4 Leu 12 Homo sapiens Human B-lymphocyte antigen CD19 precursor Differentiation antigen 685 CD19 B lymphocyte surface antigen B4 Leu 12 Homo sapiens Human Prostate, ovary testis expressed protein on chromosome 14 Ho821 mo sapiens Human Prostate, ovary testis expressed protein on chromosome 14 Ho821 mo sapiens Human Arginine-glutamic acid dipeptide repeats protein Atrophin 1 like 608 protein Atrophin 1 related protein Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human 638 Complex I intermediate associated protein 30 mitochondrial 584 precursor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly factor 1 Homo sapiens Human 167 1 2 3 4 324 1.75 756 325 1.73 326 327 328 1.72 1.72 1.67 329 1.65 330 1.65 331 332 333 334 335 336 337 338 339 1.64 1.64 1.63 1.63 1.62 1.62 1.60 1.60 1.59 340 1.59 341 1.59 342 1.59 344 345 346 1.57 1.57 1.55 347 1.54 348 1.54 349 1.54 350 1.52 351 1.50 352 1.50 Late cornified envelope protein 3C Late envelope protein 15 Small proline rich like epidermal differentiation complex protein 3A Homo sapiens Human Trefoil factor 3 precursor Intestinal trefoil factor hP1 B Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human B-lymphocyte antigen CD19 precursor Differentiation antigen CD19 B lymphocyte surface antigen B4 Leu 12 Homo sapiens Human Trefoil factor 3 precursor Intestinal trefoil factor hP1 B Homo sapiens Human Trefoil factor 3 precursor Intestinal trefoil factor hP1 B Homo sapiens Human L-myc-1 proto oncogene protein Homo sapiens Human L-myc-1 proto oncogene protein Homo sapiens Human Sex comb on midleg like protein 1 Homo sapiens Human Sex comb on midleg like protein 1 Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human Uncharacterized protein KIAA0280 Homo sapiens Human Uncharacterized protein KIAA0280 Homo sapiens Human Regenerating islet derived protein 4 precursor Reg IV REG like protein Gastrointestinal secretory protein Homo sapiens Human Regenerating islet derived protein 4 precursor Reg IV REG like protein Gastrointestinal secretory protein Homo sapiens Human Regenerating islet derived protein 4 precursor Reg IV REG like protein Gastrointestinal secretory protein Homo sapiens Human Regenerating islet derived protein 4 precursor Reg IV REG like protein Gastrointestinal secretory protein Homo sapiens Human Transmembrane protein 106B Homo sapiens Human Transmembrane protein 106B Homo sapiens Human Regenerating islet derived protein 4 precursor Reg IV REG like protein Gastrointestinal secretory protein Homo sapiens Human Regenerating islet derived protein 4 precursor Reg IV REG like protein Gastrointestinal secretory protein Homo sapiens Human Regenerating islet derived protein 4 precursor Reg IV REG like protein Gastrointestinal secretory protein Homo sapiens Human Regenerating islet derived protein 4 precursor Reg IV REG like protein Gastrointestinal secretory protein Homo sapiens Human Regenerating islet derived protein 4 precursor Reg IV REG like protein Gastrointestinal secretory protein Homo sapiens Human Regenerating islet derived protein 4 precursor Reg IV REG like protein Gastrointestinal secretory protein Homo sapiens Human Regenerating islet derived protein 4 precursor Reg IV REG like protein Gastrointestinal secretory protein Homo sapiens Human 619 1320 1320 965 425 425 690 690 931 931 796 796 937 937 500 500 500 500 1243 1243 454 792 792 792 1435 547 547 168 1 2 3 4 353 1.48 829 354 1.48 355 1.48 356 1.47 357 358 359 1.46 1.46 1.45 360 1.45 361 1.42 362 1.42 363 364 365 1.41 1.41 1.40 366 1.39 367 1.39 368 369 1.38 1.36 370 1.35 371 372 373 1.32 1.32 1.31 374 1.31 375 1.30 Metalloproteinase inhibitor 2 precursor TIMP 2 Tissue inhibitor of metalloproteinases 2 CSC 21K Homo sapiens Human Metalloproteinase inhibitor 2 precursor TIMP 2 Tissue inhibitor of metalloproteinases 2 CSC 21K Homo sapiens Human Metalloproteinase inhibitor 2 precursor TIMP 2 Tissue inhibitor of metalloproteinases 2 CSC 21K Homo sapiens Human Bactericidal/permeability-increasing protein like 2 precursor Homo sapiens Human Transmembrane protein 39A Homo sapiens Human Transmembrane protein 39A Homo sapiens Human Chromaffin granule amine transporter Vesicular amine transporter 1 VAT1 Solute carrier family 18 member 1 Homo sapiens Human Chromaffin granule amine transporter Vesicular amine transporter 1 VAT1 Solute carrier family 18 member 1 Homo sapiens Human Regenerating islet derived protein 4 precursor Reg IV REG like protein Gastrointestinal secretory protein Homo sapiens Human Regenerating islet derived protein 4 precursor Reg IV REG like protein Gastrointestinal secretory protein Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human NADH-ubiquinone oxidoreductase chain 1 EC 1 6 5 3 NADH dehydrogenase subunit 1 Homo sapiens Human Late cornified envelope protein 3C Late envelope protein 15 Small proline rich like epidermal differentiation complex protein 3A Homo sapiens Human Late cornified envelope protein 3C Late envelope protein 15 Small proline rich like epidermal differentiation complex protein 3A Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human Complex I intermediate associated protein 30 mitochondrial precursor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly factor 1 Homo sapiens Human Late cornified envelope protein 3C Late envelope protein 15 Small proline rich like epidermal differentiation complex protein 3A Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human Regenerating islet derived protein 4 precursor Reg IV REG like protein Gastrointestinal secretory protein Homo sapiens Human Regenerating islet derived protein 4 precursor Reg IV REG like protein Gastrointestinal secretory protein Homo sapiens Human Zinc finger protein 350 Zinc finger protein ZBRK1 Zinc finger and BRCA1 interacting protein with a KRAB domain 1 KRAB zinc finger protein ZFQR Homo sapiens Human 829 829 1294 427 427 1076 1076 509 509 722 722 855 777 777 1098 482 394 726 726 577 577 830 169 1 2 3 4 376 1.30 830 377 1.30 378 1.29 379 1.28 380 1.27 381 382 383 384 385 386 1.26 1.26 1.25 1.22 1.20 1.19 387 1.16 388 1.16 389 1.14 390 1.14 391 1.12 392 1.12 393 1.12 394 1.10 395 1.10 396 397 398 1.09 1.08 1.05 Zinc finger protein 350 Zinc finger protein ZBRK1 Zinc finger and BRCA1 interacting protein with a KRAB domain 1 KRAB zinc finger protein ZFQR Homo sapiens Human Zinc finger protein 350 Zinc finger protein ZBRK1 Zinc finger and BRCA1 interacting protein with a KRAB domain 1 KRAB zinc finger protein ZFQR Homo sapiens Human Complex I intermediate associated protein 30 mitochondrial precursor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly factor 1 Homo sapiens Human Replication protein A 14 kDa subunit RP A RF A Replication factor A protein 3 p14 Homo sapiens Human Collagen alpha 1 VIII chain precursor Endothelial collagen Homo sapiens Human 40S ribosomal protein S29 Homo sapiens Human 40S ribosomal protein S29 Homo sapiens Human Optic atrophy 3 protein Homo sapiens Human Transmembrane protein 78 Homo sapiens Human C4b-binding protein beta chain precursor Homo sapiens Human Uncharacterized protein C20orf54 precursor Homo sapiens Human Complex I intermediate associated protein 30 mitochondrial precursor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly factor 1 Homo sapiens Human Complex I intermediate associated protein 30 mitochondrial precursor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly factor 1 Homo sapiens Human Complex I intermediate associated protein 30 mitochondrial precursor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly factor 1 Homo sapiens Human Complex I intermediate associated protein 30 mitochondrial precursor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly factor 1 Homo sapiens Human Zinc finger HIT domain containing protein 1 Cyclin G1 binding protein 1 Homo sapiens Human Zinc finger HIT domain containing protein 1 Cyclin G1 binding protein 1 Homo sapiens Human Zinc finger HIT domain containing protein 1 Cyclin G1 binding protein 1 Homo sapiens Human Metalloproteinase inhibitor 2 precursor TIMP 2 Tissue inhibitor of metalloproteinases 2 CSC 21K Homo sapiens Human Metalloproteinase inhibitor 2 precursor TIMP 2 Tissue inhibitor of metalloproteinases 2 CSC 21K Homo sapiens Human UPF0184 protein C9orf16 EST00098 Homo sapiens Human Melanocortin receptor 4 MC4 R Homo sapiens Human Epididymal-specific lipocalin 9 precursor MUP like lipocalin Homo sapiens Human 830 406 678 1095 1055 1055 1304 961 857 980 489 489 626 626 684 684 684 853 853 974 982 957 170 1 2 3 4 399 1.04 823 400 1.04 401 1.04 402 1.04 403 1.03 404 1.03 405 1.00 406 1.00 407 0.97 408 0.97 409 410 411 412 0.96 0.96 0.96 0.95 413 0.95 414 0.94 415 0.94 416 0.94 417 0.93 418 0.93 Hemoglobin subunit epsilon Hemoglobin epsilon chain Epsilon globin Homo sapiens Human Hemoglobin subunit epsilon Hemoglobin epsilon chain Epsilon globin Homo sapiens Human Hemoglobin subunit epsilon Hemoglobin epsilon chain Epsilon globin Homo sapiens Human Hemoglobin subunit epsilon Hemoglobin epsilon chain Epsilon globin Homo sapiens Human Cardiotrophin-like cytokine factor 1 precursor B cell stimulating factor 3 BSF 3 Novel neurotrophin 1 NNT 1 Homo sapiens Human Cardiotrophin-like cytokine factor 1 precursor B cell stimulating factor 3 BSF 3 Novel neurotrophin 1 NNT 1 Homo sapiens Human NACHT, LRR and PYD containing protein 11 PYRIN containing APAF1 like protein 6 Nucleotide binding oligomerization domain protein 17 Homo sapiens Human NACHT, LRR and PYD containing protein 11 PYRIN containing APAF1 like protein 6 Nucleotide binding oligomerization domain protein 17 Homo sapiens Human Beta-defensin 131 precursor Defensin beta 131 Beta defensin 31 DEFB 31 Homo sapiens Human Beta-defensin 131 precursor Defensin beta 131 Beta defensin 31 DEFB 31 Homo sapiens Human Beta-tectorin precursor Homo sapiens Human Beta-tectorin precursor Homo sapiens Human Beta-tectorin precursor Homo sapiens Human Chromaffin granule amine transporter Vesicular amine transporter 1 VAT1 Solute carrier family 18 member 1 Homo sapiens Human Chromaffin granule amine transporter Vesicular amine transporter 1 VAT1 Solute carrier family 18 member 1 Homo sapiens Human Arginine-glutamic acid dipeptide repeats protein Atrophin 1 like protein Atrophin 1 related protein Homo sapiens Human Arginine-glutamic acid dipeptide repeats protein Atrophin 1 like protein Atrophin 1 related protein Homo sapiens Human Arginine-glutamic acid dipeptide repeats protein Atrophin 1 like protein Atrophin 1 related protein Homo sapiens Human Complex I intermediate associated protein 30 mitochondrial precursor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly factor 1 Homo sapiens Human Complex I intermediate associated protein 30 mitochondrial precursor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly factor 1 Homo sapiens Human 823 823 823 989 989 814 814 955 955 920 920 920 716 716 587 587 587 562 562 171 1 2 419 0.93 420 421 0.91 0.89 422 0.89 423 0.89 424 0.88 425 0.86 426 0.85 427 0.84 428 0.84 429 430 0.83 0.82 431 0.82 432 0.81 433 0.79 434 435 436 437 0.78 0.78 0.78 0.77 438 0.75 439 0.75 440 0.74 441 0.74 442 0.73 3 4 Complex I intermediate associated protein 30 mitochondrial 562 precursor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly factor 1 Homo sapiens Human Serine/threonine-protein 911 Beta-defensin 131 precursor Defensin beta 131 Beta defensin 31 963 DEFB 31 Homo sapiens Human Beta-defensin 131 precursor Defensin beta 131 Beta defensin 31 963 DEFB 31 Homo sapiens Human Beta-defensin 131 precursor Defensin beta 131 Beta defensin 31 963 DEFB 31 Homo sapiens Human Collagen alpha 1 VIII chain precursor Endothelial collagen 720 Homo sapiens Human Apolipoprotein C III precursor Apo CIII ApoC III Homo sa862 piens Human Growth hormone releasing hormone receptor precursor GHRH 947 receptor GRF receptor GRFR Homo sapiens Human Glycine cleavage system H protein mitochondrial precursor 729 Homo sapiens Human Glycine cleavage system H protein mitochondrial precursor 729 Homo sapiens Human NEDD4 1492 B-lymphocyte antigen CD19 precursor Differentiation antigen 834 CD19 B lymphocyte surface antigen B4 Leu 12 Homo sapiens Human B-lymphocyte antigen CD19 precursor Differentiation antigen 834 CD19 B lymphocyte surface antigen B4 Leu 12 Homo sapiens Human Protein S100 A14 S100 calcium binding protein A14 S114 979 Homo sapiens Human Protein S100 A14 S100 calcium binding protein A14 S114 977 Homo sapiens Human L-myc-1 proto oncogene protein Homo sapiens Human 700 L-myc-1 proto oncogene protein Homo sapiens Human 700 L-myc-1 proto oncogene protein Homo sapiens Human 700 Relaxin-3 precursor Prorelaxin H3 Insulin like peptide INSL7 986 Insulin like peptide 7 Contains Relaxin 3 B chain Relaxin 3 A chain Homo sapiens Human Regenerating islet derived protein 4 precursor Reg IV REG like 510 protein Gastrointestinal secretory protein Homo sapiens Human Regenerating islet derived protein 4 precursor Reg IV REG like 510 protein Gastrointestinal secretory protein Homo sapiens Human Dopamine- and cAMP regulated neuronal phosphoprotein 703 DARPP 32 Homo sapiens Human Dopamine- and cAMP regulated neuronal phosphoprotein 703 DARPP 32 Homo sapiens Human Metalloproteinase inhibitor 2 precursor TIMP 2 Tissue inhibitor 946 of metalloproteinases 2 CSC 21K Homo sapiens Human 172 1 2 3 4 443 0.73 946 444 0.72 445 0.72 446 0.72 447 0.72 448 0.71 449 0.71 450 0.70 451 0.70 452 0.68 453 0.68 454 455 456 0.66 0.66 0.65 457 0.65 458 0.65 459 0.64 460 0.64 461 0.63 462 463 464 0.62 0.62 0.61 465 0.61 Metalloproteinase inhibitor 2 precursor TIMP 2 Tissue inhibitor of metalloproteinases 2 CSC 21K Homo sapiens Human Integrin-linked protein kinase EC 2 7 11 1 ILK 1 ILK 2 59 kDa serine threonine protein kinase p59ILK Homo sapiens Human Integrin-linked protein kinase EC 2 7 11 1 ILK 1 ILK 2 59 kDa serine threonine protein kinase p59ILK Homo sapiens Human Integrin-linked protein kinase EC 2 7 11 1 ILK 1 ILK 2 59 kDa serine threonine protein kinase p59ILK Homo sapiens Human Integrin-linked protein kinase EC 2 7 11 1 ILK 1 ILK 2 59 kDa serine threonine protein kinase p59ILK Homo sapiens Human Replication protein A 14 kDa subunit RP A RF A Replication factor A protein 3 p14 Homo sapiens Human Replication protein A 14 kDa subunit RP A RF A Replication factor A protein 3 p14 Homo sapiens Human B-lymphocyte antigen CD19 precursor Differentiation antigen CD19 B lymphocyte surface antigen B4 Leu 12 Homo sapiens Human B-lymphocyte antigen CD19 precursor Differentiation antigen CD19 B lymphocyte surface antigen B4 Leu 12 Homo sapiens Human Zinc finger HIT domain containing protein 1 Cyclin G1 binding protein 1 Homo sapiens Human Zinc finger HIT domain containing protein 1 Cyclin G1 binding protein 1 Homo sapiens Human Ig heavy chain V III region WEA Homo sapiens Human Ig heavy chain V III region WEA Homo sapiens Human P2Y purinoceptor 1 ATP receptor P2Y1 Purinergic receptor Homo sapiens Human P2Y purinoceptor 1 ATP receptor P2Y1 Purinergic receptor Homo sapiens Human P2Y purinoceptor 1 ATP receptor P2Y1 Purinergic receptor Homo sapiens Human Ladinin 1 Lad 1 120 kDa linear IgA bullous dermatosis antigen 97 kDa linear IgA bullous dermatosis antigen Linear IgA disease antigen homolog LadA Homo sapiens Human Ladinin 1 Lad 1 120 kDa linear IgA bullous dermatosis antigen 97 kDa linear IgA bullous dermatosis antigen Linear IgA disease antigen homolog LadA Homo sapiens Human Olfactory receptor 4D10 Olfactory receptor OR11 251 Homo sapiens Human Transcription factor jun D Homo sapiens Human Transcription factor jun D Homo sapiens Human Gamma-secretase subunit APH 1B APH 1b Aph 1beta Presenilin stabilization factor like Homo sapiens Human Gamma-secretase subunit APH 1B APH 1b Aph 1beta Presenilin stabilization factor like Homo sapiens Human 490 490 490 490 677 677 831 831 732 732 661 661 697 697 697 390 390 1295 1000 1000 1059 1059 173 1 2 3 4 466 0.61 1059 467 468 469 470 471 472 473 0.60 0.60 0.60 0.60 0.60 0.60 0.59 474 0.58 475 0.58 476 0.58 477 0.57 478 0.57 479 0.57 480 0.56 481 0.56 482 0.56 483 484 485 0.54 0.54 0.53 486 0.52 487 0.52 488 0.52 489 0.52 490 0.52 Gamma-secretase subunit APH 1B APH 1b Aph 1beta Presenilin stabilization factor like Homo sapiens Human RMD5 homolog B Homo sapiens Human RMD5 homolog B Homo sapiens Human RMD5 homolog B Homo sapiens Human RMD5 homolog B Homo sapiens Human RMD5 homolog B Homo sapiens Human RMD5 homolog B Homo sapiens Human Protein FAM19A1 precursor Chemokine like protein TAFA 1 Homo sapiens Human Complex I intermediate associated protein 30 mitochondrial precursor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly factor 1 Homo sapiens Human Complex I intermediate associated protein 30 mitochondrial precursor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly factor 1 Homo sapiens Human Complex I intermediate associated protein 30 mitochondrial precursor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly factor 1 Homo sapiens Human Cathepsin L2 precursor EC 3 4 22 43 Cathepsin V Cathepsin U Homo sapiens Human Cathepsin L2 precursor EC 3 4 22 43 Cathepsin V Cathepsin U Homo sapiens Human Cathepsin L2 precursor EC 3 4 22 43 Cathepsin V Cathepsin U Homo sapiens Human Glycine cleavage system H protein mitochondrial precursor Homo sapiens Human Glycine cleavage system H protein mitochondrial precursor Homo sapiens Human Glycine cleavage system H protein mitochondrial precursor Homo sapiens Human UPF0184 protein C9orf16 EST00098 Homo sapiens Human UPF0184 protein C9orf16 EST00098 Homo sapiens Human Chromaffin granule amine transporter Vesicular amine transporter 1 VAT1 Solute carrier family 18 member 1 Homo sapiens Human Epididymal-specific lipocalin 6 precursor Lipocalin 5 Homo sapiens Human Epididymal-specific lipocalin 6 precursor Lipocalin 5 Homo sapiens Human Epididymal-specific lipocalin 6 precursor Lipocalin 5 Homo sapiens Human Epididymal-specific lipocalin 6 precursor Lipocalin 5 Homo sapiens Human Epididymal-specific lipocalin 6 precursor Lipocalin 5 Homo sapiens Human 585 585 585 585 585 585 936 1181 1181 1181 369 369 369 748 748 748 864 864 687 820 820 820 820 820 174 1 2 3 4 491 0.50 689 492 0.49 493 0.49 494 0.48 495 0.48 496 0.47 497 0.47 498 0.47 499 500 0.44 0.42 501 0.42 502 0.34 503 0.31 504 0.27 505 0.23 Glycine cleavage system H protein mitochondrial precursor Homo sapiens Human Claudin-5 Transmembrane protein deleted in VCFS TMDVCF Homo sapiens Human Claudin-5 Transmembrane protein deleted in VCFS TMDVCF Homo sapiens Human Inositol-trisphosphate 3 kinase C EC 2 7 1 127 Inositol 1 4 5 trisphosphate 3 kinase C InsP 3 kinase C IP3K C Homo sapiens Human Inositol-trisphosphate 3 kinase C EC 2 7 1 127 Inositol 1 4 5 trisphosphate 3 kinase C InsP 3 kinase C IP3K C Homo sapiens Human Tumor necrosis factor receptor superfamily member 13C B cell activating factor receptor BAFF receptor BAFF R BLyS receptor 3 CD268 antigen Homo sapiens Human Tumor necrosis factor receptor superfamily member 13C B cell activating factor receptor BAFF receptor BAFF R BLyS receptor 3 CD268 antigen Homo sapiens Human Tumor necrosis factor receptor superfamily member 13C B cell activating factor receptor BAFF receptor BAFF R BLyS receptor 3 CD268 antigen Homo sapiens Human Coiled-coil domain containing protein 25 Homo sapiens Human Glycine cleavage system H protein mitochondrial precursor Homo sapiens Human Glycine cleavage system H protein mitochondrial precursor Homo sapiens Human Leukocyte immunoglobulin like receptor subfamily A member 3 precursor Leukocyte immunoglobulin like receptor 4 LIR 4 Immunoglobulin like transcript 6 ILT 6 Monocyte inhibitory receptor HM43 HM31 CD85e antigen Homo sapiens Human NADH dehydrogenase ubiquinone 1 subunit C1 mitochondrial precursor EC 1 6 5 3 EC 1 6 99 3 NADH ubiquinone oxidoreductase KFYI subunit Complex I KFYI CI KFYI Homo sapiens Human Olfactory receptor 11H6 Olfactory receptor OR14 35 Homo sapiens Human RING finger protein 185 Homo sapiens Human 699 699 671 671 886 886 886 901 747 747 812 969 711 688 175 Ɍɚɛɥɢɰɚ 3 ȼɟɪɨɹɬɧɨɫɬɶ ʋ ɩ/ɩ ɫɨɜɩɚɞɟɧɢɹ (%) 1 2 1 100.00 2 57.65 3 41.10 4 40.65 5 6 39.41 36.18 7 8 9 10 36.11 34.71 21.77 21.58 11 21.45 12 20.45 13 17.66 14 16.80 15 16.43 16 17 16.31 15.66 18 19 14.91 14.64 20 13.76 21 13.34 ID ɛɟɥɤɨɜ ɞɥɹ CD34+ȽɋɄ (2-ɹ ɮɪɚɤɰɢɹ, 1-ɹ ɩɨɜɬɨɪɧɨɫɬɶ) ɇɨɦɟɪ ɩɹɬɧɚ 3 4 Zinc finger protein 234 Zinc finger protein HZF4 Homo sapiens Human Tyrosine-protein phosphatase non receptor type 3 EC 3 1 3 48 Protein tyrosine phosphatase H1 PTP H1 Homo sapiens Human Folylpolyglutamate synthase mitochondrial precursor EC 6 3 2 17 Folylpoly gamma glutamate synthetase FPGS Tetrahydrofolate synthase Tetrahydrofolylpolyglutamate synthase Homo sapiens Human Actin-binding Rho activating protein Striated muscle activator of Rho dependent signaling STARS Homo sapiens Human Uncharacterized protein C18orf54 precursor Homo sapiens Human Tyrosine-protein phosphatase non receptor type 3 EC 3 1 3 48 Protein tyrosine phosphatase H1 PTP H1 Homo sapiens Human Bcl-2-associated transcription factor 1 Btf Homo sapiens Human Ribosomal protein L7 like 1 Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human Bromodomain and PHD finger containing protein 3 Homo sapiens Human PR domain zinc finger protein 6 PR domain containing protein 6 Fragment Homo sapiens Human Ribonuclease H2 subunit C RNase H2 subunit C Ribonuclease HI subunit C Aicardi Goutieres syndrome 3 protein AGS3 RNase H1 small subunit Homo sapiens Human Muscleblind-like protein 2 Muscleblind like protein like Muscleblind like protein like 39 Muscleblind like protein 1 Homo sapiens Human Ribonuclease H2 subunit C RNase H2 subunit C Ribonuclease HI subunit C Aicardi Goutieres syndrome 3 protein AGS3 RNase H1 small subunit Homo sapiens Human Tyrosine-protein phosphatase non receptor type 3 EC 3 1 3 48 Protein tyrosine phosphatase H1 PTP H1 Homo sapiens Human Ribosomal protein L7 like 1 Homo sapiens Human Nuclear pore complex protein Nup153 Nucleoporin Nup153 153 kDa nucleoporin Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human Tyrosine-protein phosphatase non receptor type 3 EC 3 1 3 48 Protein tyrosine phosphatase H1 PTP H1 Homo sapiens Human Leucine-rich repeat containing protein C22orf36 Homo sapiens Human Midline-1 EC 6 3 2 Tripartite motif containing protein 18 Putative transcription factor XPRF Midin RING finger protein 59 Midline 1 RING finger protein Homo sapiens Human 509 562 567 622 501 544 448 536 623 542 610 572 518 521 540 524 490 775 539 372 406 176 1 2 3 4 22 23 24 13.20 12.83 12.72 768 881 410 25 12.43 26 12.26 27 28 11.96 11.54 29 11.52 30 10.91 31 10.81 32 10.78 33 34 10.44 10.43 35 36 10.09 9.82 37 38 9.56 9.50 39 9.15 40 41 42 43 44 9.10 8.90 8.79 8.71 8.32 45 8.24 46 8.23 47 8.17 Keratin-associated protein 21 2 Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human Mitofusin-1 EC 3 6 5 Transmembrane GTPase MFN1 Fzo homolog Homo sapiens Human Tyrosine-protein phosphatase non receptor type 3 EC 3 1 3 48 Protein tyrosine phosphatase H1 PTP H1 Homo sapiens Human Putative pre mRNA splicing factor ATP dependent RNA helicase DHX16 EC 3 6 1DEAH box protein 16 ATP dependent RNA helicase 3 Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human ER degradation enhancing alpha mannosidase like 1 Homo sapiens Human Probable phospholipid transporting ATPase IF EC 3 6 3 1 ATPase class I type 11B ATPase IR Homo sapiens Human Killer cell immunoglobulin like receptor 2DL2 precursor MHC class I NK cell receptor Natural killer associated transcript 6 NKAT 6 p58 natural killer cell receptor clone CL 43 p58 NK receptor Homo sapiens Human Actin-binding Rho activating protein Striated muscle activator of Rho dependent signaling STARS Homo sapiens Human Uroplakin-1b Uroplakin Ib UPIb Tetraspanin 20 Tspan 20 Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human Alpha-internexin Alpha Inx 66 kDa neurofilament protein Neurofilament 66 NF 66 Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human B-lymphocyte antigen precursor B lymphocyte surface antigen 721P Protein XE7 Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human Sulfite oxidase mitochondrial precursor EC 1 8 3 1 Homo sapiens Human Protein-glutamine gamma glutamyltransferase Z EC 2 3 2 13 TGase Z TGZ TG Z Transglutaminase 7 Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human ER degradation enhancing alpha mannosidase like 1 Homo sapiens Human Apolipoprotein-L6 Apolipoprotein L VI ApoL VI Homo sapiens Human Midline-1 EC 6 3 2 Tripartite motif containing protein 18 Putative transcription factor XPRF Midin RING finger protein 59 Midline 1 RING finger protein Homo sapiens Human Inositol polyphosphate multikinase EC 2 7 1 151 Inositol 1 3 4 6 tetrakisphosphate 5 kinase Homo sapiens Human 522 534 701 603 365 624 504 578 731 528 772 569 804 550 399 720 926 865 851 584 459 565 353 177 1 2 3 4 48 8.15 482 49 8.02 50 51 8.01 7.64 52 7.36 53 54 7.30 7.21 55 56 7.00 6.80 57 58 59 60 61 6.44 6.42 6.24 6.19 6.10 62 6.04 63 5.89 64 5.80 65 66 67 68 5.70 5.60 5.25 5.22 69 5.20 70 5.19 71 72 5.17 5.08 73 5.08 Probable phospholipid transporting ATPase IF EC 3 6 3 1 ATPase class I type 11B ATPase IR Homo sapiens Human Zinc finger protein 295 Zinc finger and BTB domain containing protein 21 Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human OTU domain containing protein 4 HIV 1 induced protein HIN 1 Homo sapiens Human E3 ubiquitin protein ligase RNF19 EC 6 3 2 RING finger protein 19 Dorfin Double ring finger protein p38 protein Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human Ribonuclease H2 subunit C RNase H2 subunit C Ribonuclease HI subunit C Aicardi Goutieres syndrome 3 protein AGS3 RNase H1 small subunit Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human Olfactory receptor 10A7 Olfactory receptor OR12 6 Homo sapiens Human Transferrin receptor protein 2 TfR2 Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human Visual pigment like receptor peropsin Homo sapiens Human Calcium-binding protein 2 CaBP2 Homo sapiens Human Integrin-linked protein kinase EC 2 7 11 1 ILK 1 ILK 2 59 kDa serine threonine protein kinase p59ILK Homo sapiens Human cAMP-specific 3 5 cyclic phosphodiesterase 4D EC 3 1 4 17 DPDE3 PDE43 Homo sapiens Human Complex I intermediate associated protein 30 mitochondrial precursor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly factor 1 Homo sapiens Human Nucleoside diphosphate kinase mitochondrial precursor EC 2 7 4 6 NDP kinase mitochondrial NDK nm23 H4 Nucleoside diphosphate kinase D NDPKD Homo sapiens Human Band 4 1 like protein 4A Protein NBL4 Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human Zinc finger BED domain containing protein 4 Homo sapiens Human EMILIN-2 precursor Elastin microfibril interface located protein 2 Elastin microfibril interfacer 2 Protein FOAP 10 Homo sapiens Human Trefoil factor 3 precursor Intestinal trefoil factor hP1 B Homo sapiens Human Embryonic growth differentiation factor 1 precursor GDF 1 Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human Zinc finger protein ZIC 4 Zinc finger protein of the cerebellum 4 Homo sapiens Human Zinc finger protein ZIC 4 Zinc finger protein of the cerebellum 4 Homo sapiens Human 608 945 532 615 935 558 736 742 535 829 402 427 480 581 494 601 319 719 607 434 771 500 832 587 587 178 1 2 3 4 74 75 76 5.05 5.05 4.99 790 790 368 77 4.98 78 79 4.97 4.96 80 81 4.93 4.92 82 83 84 85 86 87 4.90 4.89 4.82 4.71 4.64 4.63 88 89 4.61 4.60 90 4.60 91 4.53 92 93 94 95 96 4.52 4.52 4.45 4.40 4.39 97 98 4.27 4.25 99 4.22 100 4.19 101 4.19 102 4.17 103 4.16 Keratin-associated protein 21 2 Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human Probable phospholipid transporting ATPase IF EC 3 6 3 1 ATPase class I type 11B ATPase IR Homo sapiens Human Dysbindin domain containing protein 2 HSMNP1 Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human Olfactory receptor 10A7 Olfactory receptor OR12 6 Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human Solute carrier family 2 facilitated glucose transporter member 8 Glucose transporter type 8 Glucose transporter type X1 Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human Transmembrane protein 106B Homo sapiens Human Cathepsin E precursor EC 3 4 23 34 Homo sapiens Human Dysbindin domain containing protein 2 HSMNP1 Homo sapiens Human Uncharacterized protein C20orf62 Homo sapiens Human Inositol polyphosphate multikinase EC 2 7 1 151 Inositol 1 3 4 6 tetrakisphosphate 5 kinase Homo sapiens Human Inositol polyphosphate multikinase EC 2 7 1 151 Inositol 1 3 4 6 tetrakisphosphate 5 kinase Homo sapiens Human Regenerating islet derived protein 4 precursor Reg IV REG like protein Gastrointestinal secretory protein Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human Olfactory receptor 10A7 Olfactory receptor OR12 6 Homo sapiens Human Tumor Muscleblind-like protein 2 Muscleblind like protein like Muscleblind like protein like 39 Muscleblind like protein 1 Homo sapiens Human Zinc finger protein 250 Zinc finger protein 647 Homo sapiens Human B-lymphocyte antigen precursor B lymphocyte surface antigen 721P Protein XE7 Homo sapiens Human B-lymphocyte antigen precursor B lymphocyte surface antigen 721P Protein XE7 Homo sapiens Human Zinc finger CCHC domain containing protein 3 Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human 495 872 863 747 508 834 853 954 724 684 503 571 498 498 781 491 491 786 493 756 450 473 485 426 426 379 732 179 1 2 3 4 104 4.04 585 105 4.00 106 3.97 107 108 3.96 3.95 109 110 111 112 113 3.94 3.94 3.92 3.90 3.89 114 3.85 115 116 117 3.84 3.83 3.80 118 3.72 119 120 121 3.66 3.65 3.63 122 123 124 3.62 3.58 3.53 125 126 127 3.47 3.46 3.43 128 129 3.42 3.41 130 131 3.33 3.30 Protein S100 A13 S100 calcium binding protein A13 Homo sapiens Human Trefoil factor 3 precursor Intestinal trefoil factor hP1 B Homo sapiens Human Nuclear pore complex protein Nup153 Nucleoporin Nup153 153 kDa nucleoporin Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human Killer cell immunoglobulin like receptor 2DL2 precursor MHC class I NK cell receptor Natural killer associated transcript 6 NKAT 6 p58 natural killer cell receptor clone CL 43 p58 NK receptor Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human Zinc finger protein 295 Zinc finger and BTB domain containing protein 21 Homo sapiens Human Treacle protein Treacher Collins syndrome protein Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human Ladinin 1 Lad 1 120 kDa linear IgA bullous dermatosis antigen 97 kDa linear IgA bullous dermatosis antigen Linear IgA disease antigen homolog LadA Homo sapiens Human Probable phospholipid transporting ATPase IF EC 3 6 3 1 ATPase class I type 11B ATPase IR Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human Retroviral-like aspartic protease 1 precursor EC 3 4 23 Skin specific retroviral like aspartic protease Skin aspartic protease SASPase TPA inducible aspartic proteinase like protein TAPS Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human UPF0193 protein EVG1 Homo sapiens Human ER degradation enhancing alpha mannosidase like 1 Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human Kynureninase EC 3 7 1 3 L kynurenine hydrolase Homo sapiens Human Transmembrane protein 106B Homo sapiens Human Complex I intermediate associated protein 30 mitochondrial precursor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly factor 1 Homo sapiens Human Secretagogin Homo sapiens Human UPF0027 protein C22orf28 Homo sapiens Human 721 364 844 356 727 727 728 952 355 484 754 746 858 630 924 861 546 927 631 510 761 738 588 716 778 620 387 180 1 2 3 4 132 3.27 570 133 3.26 134 3.26 135 3.23 136 3.23 137 3.20 138 3.19 139 140 141 3.18 3.18 3.12 142 3.08 143 144 145 3.04 3.00 2.99 146 147 2.92 2.79 148 2.75 150 2.72 151 152 153 2.70 2.69 2.69 Probable RNA binding protein 18 RNA binding motif protein 18 Homo sapiens Human Beta-1-syntrophin 59 kDa dystrophin associated protein A1 basic component 1 DAPA1B Tax interaction protein 43 TIP 43 Syntrophin 2 BSYN2 Homo sapiens Human Beta-1-syntrophin 59 kDa dystrophin associated protein A1 basic component 1 DAPA1B Tax interaction protein 43 TIP 43 Syntrophin 2 BSYN2 Homo sapiens Human Tumor necrosis factor receptor superfamily member EDAR precursor Anhidrotic ectodysplasin receptor 1 Ectodysplasin A receptor EDA A1 receptor Ectodermal dysplasia receptor Downless homolog Homo sapiens Human Tumor necrosis factor receptor superfamily member EDAR precursor Anhidrotic ectodysplasin receptor 1 Ectodysplasin A receptor EDA A1 receptor Ectodermal dysplasia receptor Downless homolog Homo sapiens Human Melanoma-associated antigen 1 MAGE 1 antigen Antigen MZ2 E Homo sapiens Human Growth/differentiation factor 3 precursor GDF 3 Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human Ubiquitin-associated domain containing protein 1 E3 ubiquitin protein ligase subunit KPC2 Kip1 ubiquitination promoting complex protein 2 Glialblastoma cell differentiation related protein 1 Homo sapiens Human SAM pointed domain containing Ets transcription factor Prostate derived Ets factor Prostate epithelium specific Ets transcription factor Prostate specific Ets Homo sapiens Human Transmembrane protein 106B Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human Complex I intermediate associated protein 30 mitochondrial precursor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly factor 1 Homo sapiens Human Claudin-17 Homo sapiens Human Complex I intermediate associated protein 30 mitochondrial precursor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly factor 1 Homo sapiens Human Olfactory receptor 4D1 Olfactory receptor TPCR16 Homo sapiens Human Late cornified envelope protein 3C Late envelope protein 15 Small proline rich like epidermal differentiation complex protein 3A Homo sapiens Human Transmembrane protein 106B Homo sapiens Human Uncharacterized protein C20orf111 Homo sapiens Human Uncharacterized protein C20orf111 Homo sapiens Human 400 400 370 370 696 594 937 937 398 576 737 744 486 436 507 394 877 616 470 470 181 1 2 3 4 154 2.66 640 155 2.60 156 2.60 157 158 2.58 2.57 159 2.52 160 2.52 161 2.49 162 163 2.47 2.43 164 2.43 165 2.42 166 2.41 167 2.37 168 2.36 169 170 2.35 2.34 171 2.33 172 2.31 173 2.30 174 2.29 175 176 177 178 2.21 2.21 2.16 2.15 179 2.15 Embryonic growth differentiation factor 1 precursor GDF 1 Homo sapiens Human cAMP-specific 3 5 cyclic phosphodiesterase 4D EC 3 1 4 17 DPDE3 PDE43 Homo sapiens Human cAMP-specific 3 5 cyclic phosphodiesterase 4D EC 3 1 4 17 DPDE3 PDE43 Homo sapiens Human Transmembrane protein 106B Homo sapiens Human Embryonic growth differentiation factor 1 precursor GDF 1 Homo sapiens Human Kallikrein-10 precursor EC 3 4 21 Protease serine like 1 Normal epithelial cell specific 1 Homo sapiens Human Kallikrein-10 precursor EC 3 4 21 Protease serine like 1 Normal epithelial cell specific 1 Homo sapiens Human Dysbindin domain containing protein 2 HSMNP1 Homo sapiens Human Beta-1,4-galactosyltransferase Protein S100 A13 S100 calcium binding protein A13 Homo sapiens Human Protein S100 A13 S100 calcium binding protein A13 Homo sapiens Human Protein S100 A13 S100 calcium binding protein A13 Homo sapiens Human Kynureninase EC 3 7 1 3 L kynurenine hydrolase Homo sapiens Human Regenerating islet derived protein 4 precursor Reg IV REG like protein Gastrointestinal secretory protein Homo sapiens Human Uroplakin-1b Uroplakin Ib UPIb Tetraspanin 20 Tspan 20 Homo sapiens Human Matrilin-4 precursor Homo sapiens Human Inner nuclear membrane protein Man1 LEM domain containing protein 3 Homo sapiens Human RNA 3 terminal phosphate cyclase EC 6 5 1 4 RNA 3 phosphate cyclase RNA cyclase Homo sapiens Human Histidine-rich glycoprotein precursor Histidine proline rich glycoprotein HPRG Homo sapiens Human ER degradation enhancing alpha mannosidase like 1 Homo sapiens Human Kynureninase EC 3 7 1 3 L kynurenine hydrolase Homo sapiens Human Coiled-coil domain containing protein 8 Homo sapiens Human Coiled-coil domain containing protein 8 Homo sapiens Human Keratin-associated protein 21 2 Homo sapiensHuman Spindle and kinetochore associated protein 2 Protein FAM33A Homo sapiens Human Spindle and kinetochore associated protein 2 Protein FAM33A Homo sapiens Human 421 421 760 469 349 349 600 391 579 579 393 499 483 407 953 548 621 530 388 396 502 502 665 589 589 182 1 2 3 4 180 2.11 685 181 182 2.08 2.07 183 2.06 184 2.04 185 2.04 186 2.03 187 188 2.01 1.99 189 1.98 190 1.97 191 1.97 192 193 194 195 196 197 1.96 1.96 1.95 1.95 1.94 1.92 198 199 1.91 1.89 200 1.81 201 202 203 1.80 1.80 1.78 204 1.76 26S protease regulatory subunit S10B Proteasome 26S subunit ATPase 6 Proteasome subunit p42 Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human Protein pellino homolog 1 Pellino 1 Pellino related intracellular signaling molecule Homo sapiens Human Ubiquitin-like protein 7 Ubiquitin like protein SB132 Bone marrow stromal cell ubiquitin like protein BMSC UbP Homo sapiens Human Achaete-scute homolog 2 Mash2 HASH2 Homo sapiens Human Achaete-scute homolog 2 Mash2 HASH2 Homo sapiens Human Embryonic growth differentiation factor 1 precursor GDF 1 Homo sapiens Human Protein FAM22G precursor Homo sapiens Human Protein S100 A13 S100 calcium binding protein A13 Homo sapiens Human Protein S100 A13 S100 calcium binding protein A13 Homo sapiens Human Late cornified envelope protein 3C Late envelope protein 15 Small proline rich like epidermal differentiation complex protein 3A Homo sapiens Human Late cornified envelope protein 3C Late envelope protein 15 Small proline rich like epidermal differentiation complex protein 3A Homo sapiens Human Ras-related protein Rab 25 CATX 8 Homo sapiens Human Ras-related protein Rab 25 CATX 8 Homo sapiens Human Serum Serum Protein yippee like 4 Homo sapiens Human Late cornified envelope protein 3C Late envelope protein 15 Small proline rich like epidermal differentiation complex protein 3A Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human Muscleblind-like protein 2 Muscleblind like protein like Muscleblind like protein like 39 Muscleblind like protein 1 Homo sapiens Human B-lymphocyte antigen CD19 precursor Differentiation antigen CD19 B lymphocyte surface antigen B4 Leu 12 Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human Synaptotagmin-15 Synaptotagmin XV SytXV Chr10Syt Homo sapiens Human Probable RNA binding protein 18 RNA binding motif protein 18 Homo sapiens Human 857 512 586 557 557 598 453 457 574 334 334 429 429 411 411 618 808 706 433 363 639 639 416 413 183 1 2 3 4 205 1.76 413 206 1.76 207 208 1.75 1.70 209 1.70 210 211 1.66 1.64 212 213 1.61 1.60 214 1.60 215 216 1.58 1.57 217 218 1.56 1.55 219 1.55 220 1.52 221 1.51 222 1.51 223 1.50 224 1.44 225 1.43 226 1.43 227 1.40 Probable RNA binding protein 18 RNA binding motif protein 18 Homo sapiens Human Probable RNA binding protein 18 RNA binding motif protein 18 Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human cAMP-dependent protein kinase inhibitor alpha PKI alpha cAMP dependent protein kinase inhibitor muscle brain isoform Homo sapiens Human cAMP-dependent protein kinase inhibitor alpha PKI alpha cAMP dependent protein kinase inhibitor muscle brain isoform Homo sapiens Human Frizzled-1 precursor Fz 1 hFz1 FzE1 Homo sapiens Human Probable RNA binding protein 18 RNA binding motif protein 18 Homo sapiens Human Calcium-binding protein 2 CaBP2 Homo sapiens Human Protein S100 A13 S100 calcium binding protein A13 Homo sapiens Human Protein S100 A13 S100 calcium binding protein A13 Homo sapiens Human Transcription factor jun D Homo sapiens Human Protein S100 A13 S100 calcium binding protein A13 Homo sapiens Human Uncharacterized protein KIAA0280 Homo sapiens Human Zinc finger protein 295 Zinc finger and BTB domain containing protein 21 Homo sapiens Human Zinc finger protein 295 Zinc finger and BTB domain containing protein 21 Homo sapiens Human DNA polymerase subunit delta 2 EC 2 7 7 7 DNA polymerase subunit delta p50 Homo sapiens Human Nasal embryonic luteinizing hormone releasing hormone factor Nasal embryonic LHRH factor Homo sapiens Human Nasal embryonic luteinizing hormone releasing hormone factor Nasal embryonic LHRH factor Homo sapiens Human Chromaffin granule amine transporter Vesicular amine transporter 1 VAT1 Solute carrier family 18 member 1 Homo sapiens Human Epididymal-specific lipocalin 6 precursor Lipocalin 5 Homo sapiens Human Ly6/PLAUR domain containing protein 3 precursor GPI anchored metastasis associated protein C4 4A homolog Matrigel induced gene C4 protein MIG C4 Homo sapiens Human Ly6/PLAUR domain containing protein 3 precursor GPI anchored metastasis associated protein C4 4A homolog Matrigel induced gene C4 protein MIG C4 Homo sapiens Human Tumor necrosis factor receptor superfamily member 19 precursor Toxicity and JNK inducer TRADE Homo sapiens Human 413 948 717 717 734 529 568 384 384 595 525 690 321 321 553 446 446 641 697 481 481 566 184 1 2 3 4 228 1.40 566 229 1.39 230 1.39 231 1.38 232 1.38 233 1.37 234 1.37 235 1.36 236 1.36 237 1.35 238 1.33 239 1.30 240 1.30 241 1.29 242 243 1.28 1.27 244 1.26 245 1.24 Tumor necrosis factor receptor superfamily member 19 precursor Toxicity and JNK inducer TRADE Homo sapiens Human UDP-N-acetylglucosamine transporter Golgi UDP GlcNAc transporter Solute carrier family 35 member A3 Homo sapiens Human UDP-N-acetylglucosamine transporter Golgi UDP GlcNAc transporter Solute carrier family 35 member A3 Homo sapiens Human Serine/threonine-protein kinase PLK3 EC 2 7 11 21 Polo like kinase 3 PLK 3 Cytokine inducible serine threonine protein kinase FGF inducible kinase Proliferation related kinase Homo sapiens Human Serine/threonine-protein kinase PLK3 EC 2 7 11 21 Polo like kinase 3 PLK 3 Cytokine inducible serine threonine protein kinase FGF inducible kinase Proliferation related kinase Homo sapiens Human Kynureninase EC 3 7 1 3 L kynurenine hydrolase Homo sapiens Human Kynureninase EC 3 7 1 3 L kynurenine hydrolase Homo sapiens Human B-lymphocyte antigen CD19 precursor Differentiation antigen CD19 B lymphocyte surface antigen B4 Leu 12 Homo sapiens Human B-lymphocyte antigen CD19 precursor Differentiation antigen CD19 B lymphocyte surface antigen B4 Leu 12 Homo sapiens Human R-spondin-1 precursor Roof plate specific spondin 1 hRspo1 Homo sapiens Human Regenerating islet derived protein 4 precursor Reg IV REG like protein Gastrointestinal secretory protein Homo sapiens Human B-lymphocyte antigen CD19 precursor Differentiation antigen CD19 B lymphocyte surface antigen B4 Leu 12 Homo sapiens Human B-lymphocyte antigen CD19 precursor Differentiation antigen CD19 B lymphocyte surface antigen B4 Leu 12 Homo sapiens Human L-lactate dehydrogenase A chain EC 1 1 1 27 LDH A LDH muscle subunit LDH M Proliferation inducing gene 19 protein Renal carcinoma antigen NY REN 59 Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human Translocator protein Peripheral type benzodiazepine receptor PBR PKBS Mitochondrial benzodiazepine receptor Homo sapiens Human WAP four disulfide core domain protein 10A precursor Putative protease inhibitor WAP10A Homo sapiens Human UPF0308 protein C9orf21 Homo sapiens Human 460 460 575 575 517 517 520 520 463 496 489 489 946 933 591 691 511 185 1 2 3 4 246 247 248 1.21 1.20 1.19 408 932 506 249 1.19 250 1.19 251 1.18 252 1.17 253 1.17 254 1.14 255 256 257 1.13 1.13 1.10 258 1.10 259 1.10 260 1.09 261 1.05 262 263 264 1.02 1.02 1.01 265 1.01 266 1.01 267 1.00 268 0.99 269 0.99 DNA polymerase beta EC 2 7 7 7 EC 4 2 99 Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human Zinc finger protein 295 Zinc finger and BTB domain containing protein 21 Homo sapiens Human Zinc finger protein 295 Zinc finger and BTB domain containing protein 21 Homo sapiens Human Zinc finger protein 295 Zinc finger and BTB domain containing protein 21 Homo sapiens Human Tumor necrosis factor receptor superfamily member 13C B cell activating factor receptor BAFF receptor BAFF R BLyS receptor 3 CD268 antigen Homo sapiens Human cAMP-dependent protein kinase inhibitor alpha PKI alpha cAMP dependent protein kinase inhibitor muscle brain isoform Homo sapiens Human cAMP-dependent protein kinase inhibitor alpha PKI alpha cAMP dependent protein kinase inhibitor muscle brain isoform Homo sapiens Human Guanine deaminase EC 3 5 4 3 Guanase Guanine aminase Guanine aminohydrolase GAH p51 nedasin Homo sapiens Human Uncharacterized protein C20orf62 Homo sapiens Human Uncharacterized protein C20orf62 Homo sapiens Human Neuronal acetylcholine receptor subunit alpha 6 precursor Homo sapiens Human Neuronal acetylcholine receptor subunit alpha 6 precursor Homo sapiens Human Neuronal acetylcholine receptor subunit alpha 6 precursor Homo sapiens Human Protein S100 A13 S100 calcium binding protein A13 Homo sapiens Human Chitinase 3 like protein 2 precursor YKL 39 Chondrocyte protein 39 Homo sapiens Human Beta-1,4-galactosyltransferase Beta-1,4-galactosyltransferase B-lymphocyte antigen precursor B lymphocyte surface antigen 721P Protein XE7 Homo sapiens Human B-lymphocyte antigen precursor B lymphocyte surface antigen 721P Protein XE7 Homo sapiens Human B-lymphocyte antigen precursor B lymphocyte surface antigen 721P Protein XE7 Homo sapiens Human B-lymphocyte antigen CD19 precursor Differentiation antigen CD19 B lymphocyte surface antigen B4 Leu 12 Homo sapiens Human UPF0384 protein CGI 117 HBV pre S2 trans regulated protein 3 Homo sapiens Human UPF0384 protein CGI 117 HBV pre S2 trans regulated protein 3 Homo sapiens Human 506 506 642 703 703 478 423 423 358 358 358 454 420 523 523 435 435 435 702 464 464 186 1 2 270 271 272 273 0.98 0.98 0.98 0.96 274 0.96 275 0.95 276 277 278 279 0.94 0.94 0.92 0.91 280 0.91 281 0.91 282 0.88 283 0.88 284 0.88 285 286 287 288 289 290 291 0.86 0.85 0.85 0.85 0.84 0.84 0.83 292 293 294 295 296 297 298 0.82 0.82 0.78 0.78 0.78 0.78 0.78 3 Visual pigment like receptor peropsin Homo sapiens Human Visual pigment like receptor peropsin Homo sapiens Human Visual pigment like receptor peropsin Homo sapiens Human Sorting nexin 18 Sorting nexin associated Golgi protein 1 SH3 and PX domain containing protein 3B Homo sapiens Human Sorting nexin 18 Sorting nexin associated Golgi protein 1 SH3 and PX domain containing protein 3B Homo sapiens Human Ubiquitin-like protein 7 Ubiquitin like protein SB132 Bone marrow stromal cell ubiquitin like protein BMSC UbP Homo sapiens Human UPF0327 protein C1orf151 Homo sapiens Human UPF0327 protein C1orf151 Homo sapiens Human Beta-tectorin precursor Homo sapiens Human Spindle and kinetochore associated protein 2 Protein FAM33A Homo sapiens Human Spindle and kinetochore associated protein 2 Protein FAM33A Homo sapiens Human Spindle and kinetochore associated protein 2 Protein FAM33A Homo sapiens Human Tumor necrosis factor receptor superfamily member EDAR precursor Anhidrotic ectodysplasin receptor 1 Ectodysplasin A receptor EDA A1 receptor Ectodermal dysplasia receptor Downless homolog Homo sapiens Human Tumor necrosis factor receptor superfamily member EDAR precursor Anhidrotic ectodysplasin receptor 1 Ectodysplasin A receptor EDA A1 receptor Ectodermal dysplasia receptor Downless homolog Homo sapiens Human Tumor necrosis factor receptor superfamily member EDAR precursor Anhidrotic ectodysplasin receptor 1 Ectodysplasin A receptor EDA A1 receptor Ectodermal dysplasia receptor Downless homolog Homo sapiens Human UPF0399 protein C6orf153 Homo sapiens Human AP-2 AP-2 AP-2 Keratin-associated protein 21 2 Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human GTP-binding protein SAR1a COPII associated small GTPase Homo sapiens Human NIPA-like protein 3 Homo sapiens Human NIPA-like protein 3 Homo sapiens Human AP-2 AP-2 AP-2 AP-2 AP-2 4 417 417 417 683 683 774 432 432 333 419 419 419 474 474 474 629 477 477 477 345 345 458 390 390 385 385 385 385 385 187 1 2 3 4 299 300 301 0.75 0.75 0.74 389 389 590 302 0.74 303 0.74 304 0.71 305 0.70 306 0.68 307 0.67 308 0.67 309 0.66 310 0.66 311 0.63 312 313 314 315 316 317 318 0.62 0.60 0.60 0.59 0.53 0.49 0.46 319 0.45 OTU domain containing protein 6A Homo sapiens Human OTU domain containing protein 6A Homo sapiens Human Neuropeptide B precursor Preproprotein L7 hPPL7 Contains Neuropeptide B 23 NPB23 hL7 Neuropeptide B 29 NPB29 hL7C Homo sapiens Human Neuropeptide B precursor Preproprotein L7 hPPL7 Contains Neuropeptide B 23 NPB23 hL7 Neuropeptide B 29 NPB29 hL7C Homo sapiens Human Neuropeptide B precursor Preproprotein L7 hPPL7 Contains Neuropeptide B 23 NPB23 hL7 Neuropeptide B 29 NPB29 hL7C Homo sapiens Human Claudin-5 Transmembrane protein deleted in VCFS TMDVCF Homo sapiens Human HIG1 domain family member 1B Protein CLST 11240 Homo sapiens Human Phosphoglycerate kinase 1 EC 2 7 2 3 Primer recognition protein 2 PRP 2 Cell migration inducing gene 10 protein Homo sapiens Human B-lymphocyte antigen CD19 precursor Differentiation antigen CD19 B lymphocyte surface antigen B4 Leu 12 Homo sapiens Human B-lymphocyte antigen CD19 precursor Differentiation antigen CD19 B lymphocyte surface antigen B4 Leu 12 Homo sapiens Human Chromaffin granule amine transporter Vesicular amine transporter 1 VAT1 Solute carrier family 18 member 1 Homo sapiens Human Chromaffin granule amine transporter Vesicular amine transporter 1 VAT1 Solute carrier family 18 member 1 Homo sapiens Human Zinc finger HIT domain containing protein 1 Cyclin G1 binding protein 1 Homo sapiens Human Uncharacterized protein C20orf108 Homo sapiens Human Calcium-binding protein 3 CaBP3 Homo sapiens Human Calcium-binding protein 3 CaBP3 Homo sapiens Human Uncharacterized protein C14orf128 Homo sapiens Human Ig heavy chain V III region TRO Homo sapiens Human Putative uncharacterized protein C8orf39 Homo sapiens Human Retroviral-like aspartic protease 1 precursor EC 3 4 23 Skin specific retroviral like aspartic protease Skin aspartic protease SASPase TPA inducible aspartic proteinase like protein TAPS Homo sapiens Human Tumor protein p73 like p73L p63 Tumor protein 63 TP63 p51 p40 Keratinocyte transcription factor KET Chronic ulcerative stomatitis protein CUSP Homo sapiens Human 590 590 779 637 627 354 354 625 625 689 664 612 612 634 465 452 643 688 188 1 2 3 4 320 0.43 787 321 322 323 324 0.42 0.39 0.35 0.31 325 0.30 326 327 328 0.26 0.25 0.15 Autophagy-related protein 7 APG7 like Ubiquitin activating enzyme E1 like protein hAGP7 Homo sapiens Human Uncharacterized protein KIAA0280 Homo sapiens Human 40S ribosomal protein S29 Homo sapiens Human Beta-1,4-galactosyltransferase Glucocorticoid modulatory element binding protein 2 GMEB 2 Parvovirus initiation factor p79 PIF p79 DNA binding protein p79PIF Homo sapiens Human Zinc finger protein 148 Zinc finger DNA binding protein 89 Transcription factor ZBP 89 Homo sapiens Human Uncharacterized protein C2orf32 Homo sapiens Human Placenta growth factor precursor PlGF Homo sapiens Human Mitochondrial ribosomal protein S23 S23mt MRP S23 Homo sapiens Human 635 467 709 650 456 687 461 471 189 Ɍɚɛɥɢɰɚ 4 ȼɟɪɨɹɬɧɨɫɬɶ ʋ ɩ/ɩ ɫɨɜɩɚɞɟɧɢɹ (%) 1 2 1 82.94 2 82.01 3 77.06 4 69.62 5 64.63 6 64.28 7 60.10 8 53.38 9 53.27 10 11 53.24 52.80 12 50.05 13 48.92 14 15 47.46 44.57 16 42.07 17 41.31 18 19 20 38.41 38.20 37.79 21 37.60 ID ɛɟɥɤɨɜ ɞɥɹ CD34+ȽɋɄ (2-ɹ ɮɪɚɤɰɢɹ, 2-ɹ ɩɨɜɬɨɪɧɨɫɬɶ) ɇɨɦɟɪ ɩɹɬɧɚ 3 4 Actin-binding Rho activating protein Striated muscle activator of Rho dependent signaling STARS Homo sapiens Human Actin-binding Rho activating protein Striated muscle activator of Rho dependent signaling STARS Homo sapiens Human Actin-binding Rho activating protein Striated muscle activator of Rho dependent signaling STARS Homo sapiens Human Immunoglobulin superfamily member 8 precursor CD81 partner 3 Glu Trp Ile EWI motif containing protein 2 EWI 2 Keratinocytes associated transmembrane protein 4 KCT 4 LIR D1 CD316 antigen Homo sapiens Human Actin-binding Rho activating protein Striated muscle activator of Rho dependent signaling STARS Homo sapiens Human Nuclear pore complex protein Nup153 Nucleoporin Nup153 153 kDa nucleoporin Homo sapiens Human Actin-binding Rho activating protein Striated muscle activator of Rho dependent signaling STARS Homo sapiens Human Nuclear pore complex protein Nup153 Nucleoporin Nup153 153 kDa nucleoporin Homo sapiens Human Actin-binding Rho activating protein Striated muscle activator of Rho dependent signaling STARS Homo sapiens Human Zinc finger protein 225 Homo sapiens Human Arginine-glutamic acid dipeptide repeats protein Atrophin 1 like protein Atrophin 1 related protein Homo sapiens Human Nuclear pore complex protein Nup153 Nucleoporin Nup153 153 kDa nucleoporin Homo sapiens Human Vacuolar protein sorting associated protein 25 hVps25 ELL associated protein of 20 kDa Dermal papilla derived protein 9 Homo sapiens Human Cullin-3 CUL 3 Homo sapiens Human Arginine-glutamic acid dipeptide repeats protein Atrophin 1 like protein Atrophin 1 related protein Homo sapiens Human Nuclear pore complex protein Nup153 Nucleoporin Nup153 153 kDa nucleoporin Homo sapiens Human Uncharacterized protein C18orf54 precursor Homo sapiens Human Bcl-2-modifying factor Homo sapiens Human Uncharacterized protein C18orf54 precursor Homo sapiens Human Nuclear pore complex protein Nup153 Nucleoporin Nup153 153 kDa nucleoporin Homo sapiens Human Zinc finger BED domain containing protein 4 Homo sapiens Human 12289 12354 12354 12354 12354 12354 12334 12344 12548 12576 12611 12419 12419 12419 12539 12539 12504 12324 12515 12602 12605 190 1 2 3 4 22 36.31 12490 23 35.18 24 34.54 25 33.64 26 31.87 27 28.92 28 27.46 29 25.19 30 24.98 31 24.76 32 24.00 33 23.75 34 22.57 35 21.79 36 21.75 37 21.59 38 21.48 39 20.86 40 41 20.12 20.04 42 19.72 43 44 19.48 19.44 Actin-binding Rho activating protein Striated muscle activator of Rho dependent signaling STARS Homo sapiens Human Nuclear pore complex protein Nup153 Nucleoporin Nup153153 kDa nucleoporin Homo sapiens Human Arginine-glutamic acid dipeptide repeats protein Atrophin 1 like protein Atrophin 1 related protein Homo sapiens Human Actin-binding Rho activating protein Striated muscle activator of Rho dependent signaling STARS Homo sapiens Human Uncharacterized protein C18orf54 precursor Homo sapiens Human Actin-binding Rho activating protein Striated muscle activator of Rho dependent signaling STARS Homo sapiens Human Zinc finger protein 250 Zinc finger protein 647 Homo sapiens Human Vacuolar protein sorting associated protein 25 hVps25 ELL associated protein of 20 kDa Dermal papilla derived protein 9 Homo sapiens Human Transcription factor MafK Erythroid transcription factor NF E2 p18 subunit Homo sapiens Human Actin-binding Rho activating protein Striated muscle activator of Rho dependent signaling STARS Homo sapiens Human Nuclear pore complex protein Nup153 Nucleoporin Nup153 153 kDa nucleoporin Homo sapiens Human Protein phosphatase Slingshot homolog 2 EC 3 1 3 48 EC 3 1 3 16 SSH 2L hSSH 2L Homo sapiens Human Nuclear pore complex protein Nup153 Nucleoporin Nup153 153 kDa nucleoporin Homo sapiens Human Dihydropyridine-sensitive L type calcium channel subunits alpha 2 delta precursor Contains L type calcium channel subunit alpha 2 L type calcium channel subunit delta Homo sapiens Human Actin-binding Rho activating protein Striated muscle activator of Rho dependent signaling STARS Homo sapiens Human Nuclear pore complex protein Nup153 Nucleoporin Nup153 153 kDa nucleoporin Homo sapiens Human Actin-binding Rho activating protein Striated muscle activator of Rho dependent signaling STARS Homo sapiens Human Arginine-glutamic acid dipeptide repeats protein Atrophin 1 like protein Atrophin 1 related protein Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human Glial fibrillary acidic protein astrocyte GFAP Homo sapiens Human Arginine-glutamic acid dipeptide repeats protein Atrophin 1 like protein Atrophin 1 related protein Homo sapiens Human Uncharacterized protein C21orf93 Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human 12490 12276 12276 12276 12276 12276 12276 12276 12276 12276 12276 12276 12276 12276 12517 12517 12484 12321 12285 12285 12285 12285 191 1 2 3 4 45 18.82 12285 46 18.59 47 18.52 48 17.87 49 17.47 50 17.18 51 17.07 52 16.15 53 16.08 54 16.05 55 15.93 56 15.50 57 15.38 58 15.34 59 15.13 60 61 14.84 14.80 62 14.71 63 14.52 64 14.43 65 14.35 Px19-like protein 25 kDa protein of relevant evolutionary and lymphoid interest PRELI Homo sapiens Human Uncharacterized protein C18orf54 precursor Homo sapiens Human Actin-binding Rho activating protein Striated muscle activator of Rho dependent signaling STARS Homo sapiens Human Cadherin-like protein 26 precursor Cadherin like protein VR20 Homo sapiens Human Zinc finger BED domain containing protein 4 Homo sapiens Human Uncharacterized protein C18orf54 precursor Homo sapiens Human Actin-binding Rho activating protein Striated muscle activator of Rho dependent signaling STARS Homo sapiens Human Actin-binding Rho activating protein Striated muscle activator of Rho dependent signaling STARS Homo sapiens Human Nuclear pore complex protein Nup153 Nucleoporin Nup153 153 kDa nucleoporin Homo sapiens Human Inositol polyphosphate multikinase EC 2 7 1 151 Inositol 1 3 4 6 tetrakisphosphate 5 kinase Homo sapiens Human F-box/LRR-repeat protein 2 F box and leucine rich repeat protein 2 F box protein FBL2 FBL3 Homo sapiens Human Immunoglobulin superfamily member 8 precursor CD81 partner 3 Glu Trp Ile EWI motif containing protein 2 EWI 2 Keratinocytes associated transmembrane protein 4 KCT 4 LIR D1 CD316 antigen Homo sapiens Human Arginine-glutamic acid dipeptide repeats protein Atrophin 1 like protein Atrophin 1 related protein Homo sapiens Human Tyrosine-protein phosphatase non receptor type 23 EC 3 1 3 48 His domain containing protein tyrosine phosphatase HD PTP Protein tyrosine phosphatase TD14 PTP TD14 Homo sapiens Human Px19-like protein 25 kDa protein of relevant evolutionary and lymphoid interest PRELI Homo sapiens Human Bcl-2-modifying factor Homo sapiens Human Actin-binding Rho activating protein Striated muscle activator of Rho dependent signaling STARS Homo sapiens Human Actin-binding Rho activating protein Striated muscle activator of Rho dependent signaling STARS Homo sapiens Human Selenocysteine-specific elongation factor Elongation factor sec Eukaryotic elongation factor selenocysteine tRNA specific Homo sapiens Human Cadherin-like protein 26 precursor Cadherin like protein VR20 Homo sapiens Human Actin-binding Rho activating protein Striated muscle activator of Rho dependent signaling STARS Homo sapiens Human 12285 12285 12285 12427 12612 12555 12494 12359 12359 12433 12208 12208 12208 12208 12208 12208 12208 12208 12208 12208 192 1 2 3 4 66 14.12 12208 67 13.68 68 13.61 69 13.59 70 13.22 71 72 13.19 13.15 73 13.12 74 13.11 75 13.00 76 12.83 77 12.71 78 12.70 79 12.46 80 12.33 81 12.30 82 83 12.05 11.98 84 85 11.87 11.77 86 87 11.69 11.62 Mitochondrial intermediate peptidase mitochondrial precursor EC 3 4 24 59 MIP Homo sapiens Human Arginine-glutamic acid dipeptide repeats protein Atrophin 1 like protein Atrophin 1 related protein Homo sapiens Human Actin-binding Rho activating protein Striated muscle activator of Rho dependent signaling STARS Homo sapiens Human Ubiquitin carboxyl terminal hydrolase 42 EC 3 1 2 15 Ubiquitin thioesterase 42 Ubiquitin specific processing protease 42 Deubiquitinating enzyme 42 Homo sapiens Human Immunoglobulin superfamily member 8 precursor CD81 partner 3 Glu Trp Ile EWI motif containing protein 2 EWI 2 Keratinocytes associated transmembrane protein 4 KCT 4 LIR D1 CD316 antigen Homo sapiens Human Bcl-2-modifying factor Homo sapiens Human Nuclear pore complex protein Nup153 Nucleoporin Nup153 153 kDa nucleoporin Homo sapiens Human Low-density lipoprotein receptor related protein 8 precursor Apolipoprotein E receptor 2 Homo sapiens Human Arginine-glutamic acid dipeptide repeats protein Atrophin 1 like protein Atrophin 1 related protein Homo sapiens Human Zinc finger BED domain containing protein 4 Homo sapiens Human Reticulon-2 Neuroendocrine specific protein like 1 NSP like protein 1 NSPLI Homo sapiens Human Nuclear pore complex protein Nup153 Nucleoporin Nup153 153 kDa nucleoporin Homo sapiens Human Vacuolar protein sorting associated protein 25 hVps25 ELL associated protein of 20 kDa Dermal papilla derived protein 9 Homo sapiens Human Nuclear pore complex protein Nup153 Nucleoporin Nup153 153 kDa nucleoporin Homo sapiens Human Zinc finger BED domain containing protein 4 Homo sapiens Human Killer cell immunoglobulin like receptor 2DL2 precursor MHC class I NK cell receptor Natural killer associated transcript 6 NKAT 6 p58 natural killer cell receptor clone CL 43 p58 NK receptor Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human Actin-binding Rho activating protein Striated muscle activator of Rho dependent signaling STARS Homo sapiens Human Complement factor H precursor H factor 1 Homo sapiens Human Actin-binding Rho activating protein Striated muscle activator of Rho dependent signaling STARS Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human Probable phospholipid transporting ATPase IF EC 3 6 3 1 ATPase class I type 11B ATPase IR Homo sapiens Human 12208 12208 12208 12375 12521 12341 12514 12622 12381 12381 12381 12381 12381 12381 12381 12381 12381 12381 12381 12381 12381 193 1 2 3 4 88 89 11.48 11.34 12381 12381 90 11.28 91 11.28 92 10.93 93 10.85 94 10.79 95 10.74 96 10.53 97 10.49 98 10.44 99 10.32 100 10.14 101 10.14 102 10.03 103 9.80 104 9.66 105 106 9.57 9.45 107 9.43 108 9.33 109 9.32 Bcl-2-modifying factor Homo sapiens Human Actin-binding Rho activating protein Striated muscle activator of Rho dependent signaling STARS Homo sapiens Human Actin-binding Rho activating protein Striated muscle activator of Rho dependent signaling STARS Homo sapiens Human Actin-binding Rho activating protein Striated muscle activator of Rho dependent signaling STARS Homo sapiens Human Transcription factor MafK Erythroid transcription factor NF E2 p18 subunit Homo sapiens Human Actin-binding Rho activating protein Striated muscle activator of Rho dependent signaling STARS Homo sapiens Human Olfactory receptor 4D1 Olfactory receptor TPCR16 Homo sapiens Human Actin-binding Rho activating protein Striated muscle activator of Rho dependent signaling STARS Homo sapiens Human Regulator of nonsense transcripts 3A Nonsense mRNA reducing factor 3A Up frameshift suppressor 3 homolog A hUpf3 Homo sapiens Human Nuclear pore complex protein Nup153 Nucleoporin Nup153 153 kDa nucleoporin Homo sapiens Human Actin-binding Rho activating protein Striated muscle activator of Rho dependent signaling STARS Homo sapiens Human Interphotoreceptor matrix proteoglycan 1 precursor Interphotoreceptor matrix proteoglycan of 150 kDa IPM 150 Sialoprotein associated with cones and rods Homo sapiens Human Reticulon-2 Neuroendocrine specific protein like 1 NSP like protein 1 NSPLI Homo sapiens Human Reticulon-2 Neuroendocrine specific protein like 1 NSP like protein 1 NSPLI Homo sapiens Human Transcription factor MafK Erythroid transcription factor NF E2 p18 subunit Homo sapiens Human Ubiquitin carboxyl terminal hydrolase 42 EC 3 1 2 15 Ubiquitin thioesterase 42 Ubiquitin specific processing protease 42 Deubiquitinating enzyme 42 Homo sapiens Human Zinc finger MYM type protein 3 Zinc finger protein 261 Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human E3 ubiquitin protein ligase RNF19 EC 6 3 2 RING finger protein 19 Dorfin Double ring finger protein p38 protein Homo sapiens Human Mannose-binding protein C precursor MBP C MBP1 Mannan binding protein Mannose binding lectin Homo sapiens Human Zinc finger BED domain containing protein 4 Homo sapiens Human Reticulon-2 Neuroendocrine specific protein like 1 NSP like protein 1 NSPLI Homo sapiens Human 12381 12381 12381 12381 12381 12381 12381 12381 12381 12381 12381 12381 12482 12313 12394 12459 12558 12325 12325 12325 194 1 2 3 4 110 111 9.20 9.18 12325 12325 112 9.16 113 114 8.94 8.93 115 8.93 116 8.78 117 118 119 120 121 8.69 8.62 8.56 8.44 8.40 122 8.29 123 124 8.28 8.27 125 8.22 126 127 8.07 7.96 128 129 130 131 7.87 7.75 7.75 7.69 132 7.68 133 7.55 134 7.51 135 7.46 136 7.41 Zinc finger protein 225 Homo sapiens Human Oligodendrocyte transcription factor 1 Oligo1 Homo sapiens Human Potassium voltage gated channel subfamily KQT member 5 Voltage gated potassium channel subunit Kv7 5 Potassium channel subunit alpha KvLQT5 KQT like 5 Homo sapiens Human Uncharacterized protein C2orf21 Homo sapiens Human Nuclear pore complex protein Nup153 Nucleoporin Nup153 153 kDa nucleoporin Homo sapiens Human Nuclear pore complex protein Nup153 Nucleoporin Nup153 153 kDa nucleoporin Homo sapiens Human Complex I intermediate associated protein 30 mitochondrial precursor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly factor 1 Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human Killer RMD5 homolog B Homo sapiens Human Inositol polyphosphate multikinase EC 2 7 1 151 Inositol 1 3 4 6 tetrakisphosphate 5 kinase Homo sapiens Human Nuclear pore complex protein Nup153 Nucleoporin Nup153 153 kDa nucleoporin Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human Glial fibrillary acidic protein astrocyte GFAP Homo sapiens Human Actin-binding Rho activating protein Striated muscle activator of Rho dependent signaling STARS Homo sapiens Human Calmegin precursor Homo sapiens Human Actin-binding Rho activating protein Striated muscle activator of Rho dependent signaling STARS Homo sapiens Human Bcl-2-modifying factor Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human Transcription factor MafK Erythroid transcription factor NF E2 p18 subunit Homo sapiens Human Suppressor of cytokine signaling 6 SOCS 6 Suppressor of cytokine signaling 4 SOCS 4 Cytokine inducible SH2 protein 4 CIS 4 Homo sapiens Human Aldehyde dehydrogenase dimeric NADP preferring EC 1 2 1 5 ALDH class 3 ALDHIII Homo sapiens Human Reticulon-2 Neuroendocrine specific protein like 1 NSP like protein 1 NSPLI Homo sapiens Human Transcription factor MafK Erythroid transcription factor NF E2 p18 subunit Homo sapiens Human Fibroblast growth factor 22 precursor FGF 22 Homo sapiens Human 12634 12634 12634 12275 12275 12254 12254 12254 12577 12607 12546 12225 12492 12357 12357 12520 12299 12470 12610 12596 12272 12272 12272 12440 12234 195 1 2 3 4 137 7.35 12234 138 7.21 139 7.17 140 7.00 141 6.96 142 6.80 143 144 6.69 6.55 145 146 6.48 6.40 147 6.38 148 6.25 149 6.07 150 6.06 151 6.06 152 6.04 153 5.98 154 5.98 155 5.93 156 5.90 157 158 159 160 161 5.89 5.84 5.83 5.78 5.76 Reticulon-2 Neuroendocrine specific protein like 1 NSP like protein 1 NSPLI Homo sapiens Human Arginine-glutamic acid dipeptide repeats protein Atrophin 1 like protein Atrophin 1 related protein Homo sapiens Human Uncharacterized protein C18orf54 precursor Homo sapiens Human Nuclear pore complex protein Nup153 Nucleoporin Nup153 153 kDa nucleoporin Homo sapiens Human Arginine-glutamic acid dipeptide repeats protein Atrophin 1 like protein Atrophin 1 related protein Homo sapiens Human Fibroblast growth factor 22 precursor FGF 22 Homo sapiens Human Bcl-2-modifying factor Homo sapiens Human Keratin, type I cytoskeletal 9 Cytokeratin 9 CK 9 Keratin 9 K9 Homo sapiens Human Bcl-2-modifying factor Homo sapiens Human Oligodendrocyte transcription factor 1 Oligo1 Homo sapiens Human Gamma crystallin C Gamma crystallin 2 1 Gamma crystallin 3 Homo sapiens Human Regenerating islet derived protein 4 precursor Reg IV REG like protein Gastrointestinal secretory protein Homo sapiens Human Actin-binding Rho activating protein Striated muscle activator of Rho dependent signaling STARS Homo sapiens Human Nuclear pore complex protein Nup153 Nucleoporin Nup153 153 kDa nucleoporin Homo sapiens Human Nuclear pore complex protein Nup153 Nucleoporin Nup153 153 kDa nucleoporin Homo sapiens Human Uncharacterized protein C18orf54 precursor Homo sapiens Human Zinc finger protein 250 Zinc finger protein 647 Homo sapiens Human Zinc finger protein 250 Zinc finger protein 647 Homo sapiens Human Aldehyde dehydrogenase dimeric NADP preferring EC 1 2 1 5 ALDH class 3 ALDHIII Homo sapiens Human Complex I intermediate associated protein 30 mitochondrial precursor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly factor 1 Homo sapiens Human Nucleolar protein 66 hsNO66 Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human Retinol dehydrogenase 13 EC 1 1 1 Homo sapiens Human Actin-binding Rho activating protein Striated muscle activator of Rho dependent signaling STARS Homo sapiens Human 12345 12426 12301 12336 12336 12336 12336 12336 12336 12432 12401 12323 12442 12481 12476 12595 12538 12613 12270 12270 12410 12410 12574 12404 196 1 2 3 4 162 5.66 12404 163 5.62 164 5.52 165 5.52 166 5.49 167 168 169 170 5.41 5.40 5.39 5.37 171 5.37 172 5.35 173 5.32 174 5.25 175 5.20 176 177 5.05 5.01 178 179 180 4.99 4.96 4.95 181 182 4.93 4.88 183 4.80 184 4.79 185 4.78 Presequence protease mitochondrial precursor EC 3 4 24 hPreP Pitrilysin metalloproteinase 1 Metalloprotease 1 hMP1 Homo sapiens Human Actin-binding Rho activating protein Striated muscle activator of Rho dependent signaling STARS Homo sapiens Human Nuclear pore complex protein Nup153 Nucleoporin Nup153 153 kDa nucleoporin Homo sapiens Human Nuclear pore complex protein Nup153 Nucleoporin Nup153 153 kDa nucleoporin Homo sapiens Human Inositol polyphosphate multikinase EC 2 7 1 151 Inositol 1 3 4 6 tetrakisphosphate 5 kinase Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human Nucleolar protein 66 hsNO66 Homo sapiens Human Zinc finger protein 225 Homo sapiens Human Complex I intermediate associated protein 30 mitochondrial precursor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly factor 1 Homo sapiens Human Complex I intermediate associated protein 30 mitochondrial precursor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly factor 1 Homo sapiens Human Zinc finger protein 250 Zinc finger protein 647 Homo sapiens Human Putative ATP dependent RNA helicase DHX33 EC 3 6 1 DEAH box protein 33 Homo sapiens Human Immunoglobulin superfamily member 8 precursor CD81 partner 3 Glu Trp Ile EWI motif containing protein 2 EWI 2 Keratinocytes associated transmembrane protein 4 KCT 4 LIR D1 CD316 antigen Homo sapiens Human Nuclear pore complex protein Nup153 Nucleoporin Nup153 153 kDa nucleoporin Homo sapiens Human Bcl-2-modifying factor Homo sapiens Human ATP-binding cassette sub family E member 1 RNase L inhibitor Ribonuclease 4 inhibitor RNS4I 2 5 oligoadenylate binding protein HuHP68 Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human ORM1-like protein 3 Homo sapiens Human Inositol polyphosphate multikinase EC 2 7 1 151 Inositol 1 3 4 6 tetrakisphosphate 5 kinase Homo sapiens Human Nucleolar protein 66 hsNO66 Homo sapiens Human Actin-binding Rho activating protein Striated muscle activator of Rho dependent signaling STARS Homo sapiens Human Nuclear pore complex protein Nup153 Nucleoporin Nup153 153 kDa nucleoporin Homo sapiens Human Zinc finger BED domain containing protein 4 Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human 12404 12404 12404 12404 12404 12404 12397 12229 12378 12429 12429 12396 12524 12322 12322 12322 12322 12322 12322 12322 12322 12376 12376 197 1 2 3 4 186 4.75 12388 187 4.72 188 4.64 189 190 4.58 4.50 191 192 4.46 4.42 193 4.38 194 4.30 195 4.28 196 4.21 197 4.21 198 4.20 199 4.12 200 4.10 201 202 4.09 4.07 203 4.05 204 4.01 205 4.01 Mucin-3B Intestinal mucin 3B Fragment Homo sapiens Human G-protein-signaling modulator 1 Activator of G protein signaling 3 Homo sapiens Human Olfactory receptor 10A7 Olfactory receptor OR12 6 Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human Arginine-glutamic acid dipeptide repeats protein Atrophin 1 like protein Atrophin 1 related protein Homo sapiens Human Uncharacterized protein C21orf62 B37 Homo sapiens Human Transcription factor MafG V maf musculoaponeurotic fibrosarcoma oncogene homolog G hMAF Homo sapiens Human Ubiquitin carboxyl terminal hydrolase 16 EC 3 1 2 15 Ubiquitin thioesterase 16 Ubiquitin specific processing protease 16 Deubiquitinating enzyme 16 Ubiquitin processing protease UBP M Homo sapiens Human Px19-like protein 25 kDa protein of relevant evolutionary and lymphoid interest PRELI Homo sapiens Human Telomeric repeat binding factor 2 TTAGGG repeat binding factor 2 Telomeric DNA binding protein Homo sapiens Human ATP-binding cassette sub family E member 1 RNase L inhibitor Ribonuclease 4 inhibitor RNS4I 2 5 oligoadenylate binding protein HuHP68 Homo sapiens Human ATP-binding cassette sub family E member 1 RNase L inhibitor Ribonuclease 4 inhibitor RNS4I 2 5 oligoadenylate binding protein HuHP68 Homo sapiens Human Inositol polyphosphate multikinase EC 2 7 1 151 Inositol 1 3 4 6 tetrakisphosphate 5 kinase Homo sapiens Human Killer cell immunoglobulin like receptor 2DL2 precursor MHC class I NK cell receptor Natural killer associated transcript 6 NKAT 6 p58 natural killer cell receptor clone CL 43 p58 NK receptorHomo sapiens Human Ladinin 1 Lad 1 120 kDa linear IgA bullous dermatosis antigen 97 kDa linear IgA bullous dermatosis antigen Linear IgA disease antigen homolog LadA Homo sapiens Human Transmembrane protein 106B Homo sapiens Human PR domain zinc finger protein 15 PR domain containing protein 15 Zinc finger protein 298 Homo sapiens Human Chondroitin sulfate glucuronyltransferase EC 2 4 1 226 N acetylgalactosaminyl proteoglycan 3 beta glucuronosyltransferase Chondroitin glucuronyltransferase II CSGlcA T Homo sapiens Human Arginine-glutamic acid dipeptide repeats protein Atrophin 1 like protein Atrophin 1 related protein Homo sapiens Human Arginine-glutamic acid dipeptide repeats protein Atrophin 1 like protein Atrophin 1 related protein Homo sapiens Human 12438 12267 12267 12267 12267 12561 12713 12590 12496 12346 12327 12588 12436 12626 12593 12402 12415 12415 12500 198 1 2 3 4 206 4.01 12352 207 3.99 208 3.98 209 3.93 210 3.93 211 3.92 212 3.91 213 3.88 214 215 3.81 3.78 216 217 3.73 3.70 218 3.70 219 220 3.68 3.67 221 3.64 222 3.64 223 3.64 224 3.63 225 3.62 226 3.59 227 3.55 Arginine-glutamic acid dipeptide repeats protein Atrophin 1 like protein Atrophin 1 related protein Homo sapiens Human Actin-binding Rho activating protein Striated muscle activator of Rho dependent signaling STARS Homo sapiens Human Ladinin 1 Lad 1 120 kDa linear IgA bullous dermatosis antigen 97 kDa linear IgA bullous dermatosis antigen Linear IgA disease antigen homolog LadA Homo sapiens Human Ankyrin repeat domain containing protein 46 Ankyrin repeat small protein ANK S Homo sapiens Human Ankyrin repeat domain containing protein 46 Ankyrin repeat small protein ANK S Homo sapiens Human Arginine-glutamic acid dipeptide repeats protein Atrophin 1 like protein Atrophin 1 related protein Homo sapiens Human Oligodendrocyte transcription factor 1 Oligo1 Homo sapiens Human Long-chain-fatty-acid--CoA ligase 6 EC 6 2 1 3 Long chain acyl CoA synthetase 6 LACS 6 Homo sapiens Human Protein yippee like 4 Homo sapiens Human E3 ubiquitin protein ligase RNF19 EC 6 3 2 RING finger protein 19 Dorfin Double ring finger protein p38 protein Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human Reticulon-2 Neuroendocrine specific protein like 1 NSP like protein 1 NSPLI Homo sapiens Human Reticulon-2 Neuroendocrine specific protein like 1 NSP like protein 1 NSPLI Homo sapiens Human Band 4 1 like protein 4A Protein NBL4 Homo sapiens Human Ladinin 1 Lad 1 120 kDa linear IgA bullous dermatosis antigen 97 kDa linear IgA bullous dermatosis antigen Linear IgA disease antigen homolog LadA Homo sapiens Human Nuclear pore complex protein Nup153 Nucleoporin Nup153 153 kDa nucleoporin Homo sapiens Human Nuclear pore complex protein Nup153 Nucleoporin Nup153 153 kDa nucleoporin Homo sapiens Human Nuclear pore complex protein Nup153 Nucleoporin Nup153 153 kDa nucleoporin Homo sapiens Human Lysosomal-associated transmembrane protein 4A Golgi 4 transmembrane spanning transporter MTP Homo sapiens Human Complex I intermediate associated protein 30 mitochondrial precursor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly factor 1 Homo sapiens Human Zinc finger BED domain containing protein 4 Homo sapiens Human Protein yippee like 4 Homo sapiens Human 12583 12307 12705 12274 12609 12383 12383 12377 12377 12377 12377 12377 12395 12585 12317 12372 12371 12277 12277 12277 12277 199 1 228 2 3.53 229 3.53 230 3.53 231 232 3.52 3.50 233 3.50 234 3.48 235 3.47 236 3.38 237 3.37 238 239 240 241 242 3.31 3.25 3.24 3.24 3.23 243 3.23 244 3.21 245 246 3.20 3.16 247 248 249 3.15 3.09 3.08 3 Probable phospholipid transporting ATPase IC EC 3 6 3 1 Familial intrahepatic cholestasis type 1 ATPase class I type 8B member 1 Homo sapiens Human Probable phospholipid transporting ATPase IC EC 3 6 3 1 Familial intrahepatic cholestasis type 1 ATPase class I type 8B member 1 Homo sapiens Human Probable phospholipid transporting ATPase IC EC 3 6 3 1 Familial intrahepatic cholestasis type 1 ATPase class I type 8B member 1 Homo sapiens Human MARVEL domain containing protein 1 Homo sapiens Human ATP-binding cassette sub family E member 1 RNase L inhibitor Ribonuclease 4 inhibitor RNS4I 2 5 oligoadenylate binding protein HuHP68 Homo sapiens Human ATP-binding cassette sub family E member 1 RNase L inhibitor Ribonuclease 4 inhibitor RNS4I 2 5 oligoadenylate binding protein HuHP68 Homo sapiens Human BAX protein cytoplasmic isoform gamma Homo sapiens Human Nuclear pore complex protein Nup153 Nucleoporin Nup153 153 kDa nucleoporin Homo sapiens Human Regenerating islet derived protein 4 precursor Reg IV REG like protein Gastrointestinal secretory protein Homo sapiens Human Telomeric repeat binding factor 2 TTAGGG repeat binding factor 2 Telomeric DNA binding protein Homo sapiens Human Transmembrane protein 106B Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human Uncharacterized protein C14orf128 Homo sapiens Human Uncharacterized protein C14orf128 Homo sapiens Human Nuclear pore complex protein Nup153 Nucleoporin Nup153 153 kDa nucleoporin Homo sapiens Human Nuclear pore complex protein Nup153 Nucleoporin Nup153 153 kDa nucleoporin Homo sapiens Human Proteasome activator complex subunit 2 Proteasome activator 28 subunit beta PA28beta PA28b Activator of multicatalytic protease subunit 2 11S regulator complex subunit beta REG beta Homo sapiens Human Sorting nexin 12 Homo sapiens Human Oligodendrocyte transcription factor 1 Oligo1 Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human Zinc finger protein 225 Homo sapiens Human Regenerating islet derived protein 4 precursor Reg IV REG like protein Gastrointestinal secretory protein Homo sapiens Human 4 12277 12277 12277 12277 12277 12353 12614 12349 12452 12712 12591 12471 12399 12430 12314 12569 12407 12407 12467 12497 12497 12309 200 1 250 2 3.02 251 3.00 252 2.95 253 2.90 254 2.89 255 2.89 256 2.88 257 2.85 258 2.80 259 2.79 260 2.78 261 262 2.73 2.71 263 2.69 264 2.67 265 2.59 266 2.54 267 2.50 268 269 270 2.49 2.45 2.45 3 Uncharacterized protein C15orf41 Protein HH114 Homo sapiens Human Ladinin 1 Lad 1 120 kDa linear IgA bullous dermatosis antigen 97 kDa linear IgA bullous dermatosis antigen Linear IgA disease antigen homolog LadA Homo sapiens Human Selenocysteine-specific elongation factor Elongation factor sec Eukaryotic elongation factor selenocysteine tRNA specific Homo sapiens Human Reticulon-2 Neuroendocrine specific protein like 1 NSP like protein 1 NSPLI Homo sapiens Human Nuclear pore complex protein Nup153 Nucleoporin Nup153 153 kDa nucleoporin Homo sapiens Human Nuclear pore complex protein Nup153 Nucleoporin Nup153 153 kDa nucleoporin Homo sapiens Human Arginine-glutamic acid dipeptide repeats protein Atrophin 1 like protein Atrophin 1 related protein Homo sapiens Human Nuclear pore complex protein Nup153 Nucleoporin Nup153 153 kDa nucleoporin Homo sapiens Human B lymphocyte activation related protein BC 1514 Homo sapiens Human Regenerating islet derived protein 4 precursor Reg IV REG like protein Gastrointestinal secretory protein Homo sapiens Human Myosin-Ia Brush border myosin I BBM I BBMI Myosin I heavy chain MIHC Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human Regulator of G protein signaling 18 RGS18 Homo sapiens Human Regenerating islet derived protein 4 precursor Reg IV REG like protein Gastrointestinal secretory protein Homo sapiens Human POU domain class 2 associating factor 1 B cell specific coactivator OBF 1 OCT binding factor 1 BOB 1 OCA B Homo sapiens Human D(2 dopamine receptor Dopamine D2 receptor Homo sapiens Human Killer cell immunoglobulin like receptor 2DL2 precursor MHC class I NK cell receptor Natural killer associated transcript 6 NKAT 6 p58 natural killer cell receptor clone CL 43 p58 NK receptor Homo sapiens Human Ladinin 1 Lad 1 120 kDa linear IgA bullous dermatosis antigen 97 kDa linear IgA bullous dermatosis antigen Linear IgA disease antigen homolog LadA Homo sapiens Human Secretagogin Homo sapiens Human Olfactomedin-like protein 1 precursor Homo sapiens Human Olfactomedin-like protein 1 precursor Homo sapiens Human 4 12403 12403 12416 12416 12416 12505 12420 12408 12443 12443 12653 12310 12589 12392 12392 12398 12579 12498 12487 12522 12533 201 1 271 272 2 2.45 2.44 273 2.34 274 2.34 275 276 277 2.31 2.27 2.24 278 2.23 279 2.23 280 2.23 281 2.23 282 283 2.15 2.07 284 2.06 285 2.03 286 2.02 287 288 289 2.01 2.00 1.90 290 1.83 291 1.83 3 Olfactomedin-like protein 1 precursor Homo sapiens Human Regenerating islet derived protein 4 precursor Reg IV REG like protein Gastrointestinal secretory protein Homo sapiens Human ER degradation enhancing alpha mannosidase like 1 Homo sapiens Human ER degradation enhancing alpha mannosidase like 1 Homo sapiens Human Protein FAM126B Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human Nuclear pore complex protein Nup153 Nucleoporin Nup153 153 kDa nucleoporin Homo sapiens Human Regulator of nonsense transcripts 3A Nonsense mRNA reducing factor 3A Up frameshift suppressor 3 homolog A hUpf3 Homo sapiens Human Regulator of nonsense transcripts 3A Nonsense mRNA reducing factor 3A Up frameshift suppressor 3 homolog A hUpf3 Homo sapiens Human Regulator of nonsense transcripts 3A Nonsense mRNA reducing factor 3A Up frameshift suppressor 3 homolog A hUpf3 Homo sapiens Human Regulator of nonsense transcripts 3A Nonsense mRNA reducing factor 3A Up frameshift suppressor 3 homolog A hUpf3 Homo sapiens Human Olfactory receptor 51T1 Homo sapiens Human Killer cell immunoglobulin like receptor 2DL2 precursor MHC class I NK cell receptor Natural killer associated transcript 6 NKAT 6 p58 natural killer cell receptor clone CL 43 p58 NK receptor Homo sapiens Human Reticulon-2 Neuroendocrine specific protein like 1 NSP like protein 1 NSPLI Homo sapiens Human Inositol polyphosphate multikinase EC 2 7 1 151 Inositol 1 3 4 6 tetrakisphosphate 5 kinase Homo sapiens Human Complex I intermediate associated protein 30 mitochondrial precursor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly factor 1 Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human Putative serum amyloid A 3 protein Homo sapiens Human Reticulon-2 Neuroendocrine specific protein like 1 NSP like protein 1 NSPLI Homo sapiens Human Neudesin precursor Neuron derived neurotrophic factor Secreted protein of unknown function SPUF protein Homo sapiens Human Neudesin precursor Neuron derived neurotrophic factor Secreted protein of unknown function SPUF protein Homo sapiens Human 4 12320 12384 12582 12615 12615 12362 12367 12367 12367 12367 12367 12367 12288 12518 12620 12198 12256 12256 12256 12256 12256 202 1 292 2 1.78 293 1.76 294 1.71 295 1.61 296 1.57 297 1.56 298 1.56 299 1.55 300 1.54 301 1.52 302 303 1.51 1.50 304 1.48 305 306 1.42 1.38 307 308 1.29 1.19 309 1.19 310 1.15 311 1.11 312 1.11 313 1.08 3 Protein phosphatase Slingshot homolog 2 EC 3 1 3 48 EC 3 1 3 16 SSH 2L hSSH 2L Homo sapiens Human Carboxypeptidase E precursor EC 3 4 17 10 CPE Carboxypeptidase H CPH Enkephalin convertase Prohormone processing carboxypeptidase Homo sapiens Human Aldose reductase EC 1 1 1 21 AR Aldehyde reductase Homo sapiens Human Px19-like protein 25 kDa protein of relevant evolutionary and lymphoid interest PRELI Homo sapiens Human Nuclear pore complex protein Nup153 Nucleoporin Nup153 153 kDa nucleoporin Homo sapiens Human Inositol polyphosphate multikinase EC 2 7 1 151 Inositol 1 3 4 6 tetrakisphosphate 5 kinase Homo sapiens Human Inositol polyphosphate multikinase EC 2 7 1 151 Inositol 1 3 4 6 tetrakisphosphate 5 kinase Homo sapiens Human UDP-N-acetylglucosamine transporter Golgi UDP GlcNAc transporter Solute carrier family 35 member A3 Homo sapiens Human Developmental pluripotency associated protein 2 Pluripotent embryonic stem cell related protein 1 Homo sapiens Human Mucin-3B Intestinal mucin 3B Fragment Homo sapiens Human Claudin-10 OSP like protein Homo sapiens Human Reticulon-2 Neuroendocrine specific protein like 1 NSP like protein 1 NSPLI Homo sapiens Human Regulator of G protein signaling 20 RGS20 Regulator of Gz selective protein signaling 1 Gz selective GTPase activating protein G z GAP Homo sapiens Human Sorting nexin 12 Homo sapiens Human Killer cell immunoglobulin like receptor 2DL2 precursor MHC class I NK cell receptor Natural killer associated transcript 6 NKAT 6 p58 natural killer cell receptor clone CL 43 p58 NK receptor Homo sapiens Human MARVEL domain containing protein 1 Homo sapiens Human Zinc/RING finger protein 4 precursor RING finger protein 204 Homo sapiens Human Zinc/RING finger protein 4 precursor RING finger protein 204 Homo sapiens Human AN1-type zinc finger protein 5 Zinc finger A20 domain containing protein 2 Zinc finger protein 216 Homo sapiens Human Putative RNA binding protein 16 RNA binding motif protein 16 Homo sapiens Human Putative RNA binding protein 16 RNA binding motif protein 16 Homo sapiens Human Actin-binding Rho activating protein Striated muscle activator of Rho dependent signaling STARS Homo sapiens Human 4 12256 12256 12256 12699 12566 12271 12271 12271 12413 12413 12413 12413 12413 12413 12413 12413 12413 12413 12308 12578 12358 12706 203 1 314 2 1.05 315 1.02 316 317 318 319 320 1.00 0.95 0.93 0.79 0.77 321 0.75 322 0.74 323 0.73 324 0.72 325 0.68 326 327 0.67 0.64 328 0.60 329 0.60 330 331 0.52 0.50 332 0.47 333 334 335 0.39 0.37 0.37 3 Tubulin polymerization promoting protein TPPP 25 kDa brain specific protein p25 alpha p24 p25 Homo sapiens Human Translocator protein Peripheral type benzodiazepine receptor PBR PKBS Mitochondrial benzodiazepine receptor Homo sapiens Human Dynamin-1-like Protein mago nashi homolog Homo sapiens Human Secretagogin Homo sapiens Human Protein yippee like 4 Homo sapiens Human Killer cell immunoglobulin like receptor 2DL2 precursor MHC class I NK cell receptor Natural killer associated transcript 6 NKAT 6 p58 natural killer cell receptor clone CL 43 p58 NK receptor Homo sapiens Human Cathepsin L2 precursor EC 3 4 22 43 Cathepsin V Cathepsin U Homo sapiens Human Homeobox protein Nkx 2 8 Homeobox protein NK 2 homolog H Homo sapiens Human DNA topoisomerase 2 binding protein 1 DNA topoisomerase II binding protein 1 DNA topoisomerase IIbeta binding protein 1 TopBP1 Homo sapiens Human Zinc finger HIT domain containing protein 1 Cyclin G1 binding protein 1 Homo sapiens Human Aldehyde dehydrogenase dimeric NADP preferring EC 1 2 1 5 ALDH class 3 ALDHIII Homo sapiens Human Microtubule-associated Arginine-glutamic acid dipeptide repeats protein Atrophin 1 like protein Atrophin 1 related protein Homo sapiens Human ER degradation enhancing alpha mannosidase like 1 Homo sapiens Human ER degradation enhancing alpha mannosidase like 1 Homo sapiens Human Oncostatin-M precursor OSM Homo sapiens Human Aldose reductase EC 1 1 1 21 AR Aldehyde reductase Homo sapiens Human Josephin-1 Josephin domain containing 1 Homo sapiens Human Transcription factor Sp4 SPR 1 Homo sapiens Human Syntaphilin Homo sapiens Human Syntaphilin Homo sapiens Human 4 12696 12284 12240 12573 12217 12217 12217 12217 12217 12217 12217 12217 12217 12217 12217 12217 12428 12428 12366 12366 12531 12604 204 Ɍɚɛɥɢɰɚ 5 ȼɟɪɨɹɬɧɨɫɬɶ ʋ ɩ/ɩ ɫɨɜɩɚɞɟɧɢɹ (%) 1 2 1 2 88.76 87.06 3 4 5 77.43 77.19 76.17 6 7 63.35 52.53 8 9 10 51.69 47.45 46.38 11 46.32 12 44.22 13 42.47 14 41.90 15 16 41.76 41.52 17 39.08 18 36.61 19 36.48 20 33.91 21 22 23 24 33.54 33.16 32.85 32.66 ID ɛɟɥɤɨɜ ɞɥɹ CD34+ȽɋɄ (3-ɹ ɮɪɚɤɰɢɹ, 1-ɹ ɩɨɜɬɨɪɧɨɫɬɶ) ɇɨɦɟɪ ɩɹɬɧɚ 3 4 Zinc finger protein 225 Homo sapiens Human Actin-binding Rho activating protein Striated muscle activator of Rho dependent signaling STARS Homo sapiens Human Cryptochrome-1 Homo sapiens Human Cryptochrome-1 Homo sapiens Human Nuclear pore complex protein Nup153 Nucleoporin Nup153 153 kDa nucleoporin Homo sapiens Human Band 4 1 like protein 4A Protein NBL4 Homo sapiens Human Beta-adrenergic receptor kinase 1 EC 2 7 11 15 Beta ARK 1 G protein coupled receptor kinase 2 Homo sapiens Human Band 4 1 like protein 4A Protein NBL4 Homo sapiens Human Cryptochrome-1 Homo sapiens Human E3 ubiquitin protein ligase HECW2 EC 6 3 2 HECT C2 and WW domain containing protein 2 NEDD4 like ubiquitin protein ligase 2 Homo sapiens Human Kinesin-like motor protein C20orf23 Sorting nexin 23 Homo sapiens Human Actin-binding Rho activating protein Striated muscle activator of Rho dependent signaling STARS Homo sapiens Human Nuclear pore complex protein Nup153 Nucleoporin Nup153 153 kDa nucleoporin Homo sapiens Human Acyl-coenzyme A thioesterase 4 EC 3 1 2 2 Acyl CoA thioesterase 4 Peroxisomal acyl coenzyme A thioester hydrolase Ib Peroxisomal long chain acyl coA thioesterase Ib PTE Ib PTE 2b Homo sapiens Human Cryptochrome-1 Homo sapiens Human Nuclear pore complex protein Nup153 Nucleoporin Nup153 153 kDa nucleoporin Homo sapiens Human Nuclear pore complex protein Nup153 Nucleoporin Nup153 153 kDa nucleoporin Homo sapiens Human Nuclear pore complex protein Nup153 Nucleoporin Nup153 153 kDa nucleoporin Homo sapiens Human DNA repair protein RAD50 EC 3 6 hRAD50 Homo sapiens Human Nuclear pore complex protein Nup153 Nucleoporin Nup153 153 kDa nucleoporin Homo sapiens Human Regulator of G protein signaling 13 RGS13 Homo sapiens Human Bcl-2-modifying factor Homo sapiens Human Regulator of G protein signaling 13 RGS13 Homo sapiens Human Arginine-glutamic acid dipeptide repeats protein Atrophin 1 like protein Atrophin 1 related protein Homo sapiens Human 504 711 209 73 588 210 231 604 97 353 226 695 519 201 267 561 616 554 240 292 233 574 221 603 205 1 2 3 4 25 32.62 898 26 32.27 27 30.86 28 29 30.70 29.52 30 31 28.05 27.92 32 27.33 33 27.15 34 35 25.83 25.02 36 24.23 37 38 23.51 23.50 39 23.22 40 23.16 41 22.90 42 22.25 43 21.72 44 45 21.08 21.04 46 20.83 47 20.45 48 19.69 Arginine-glutamic acid dipeptide repeats protein Atrophin 1 like protein Atrophin 1 related protein Homo sapiens Human Kinesin-like protein KIF3A Microtubule plus end directed kinesin motor 3A Homo sapiens Human Actin-binding Rho activating protein Striated muscle activator of Rho dependent signaling STARS Homo sapiens Human Bcl-2-modifying factor Homo sapiens Human Suppressor of cytokine signaling 6 SOCS 6 Suppressor of cytokine signaling 4 SOCS 4 Cytokine inducible SH2 protein 4 CIS 4 Homo sapiens Human Band 4 1 like protein 4A Protein NBL4 Homo sapiens Human Glial fibrillary acidic protein astrocyte GFAP Homo sapiens Human Kinesin-like protein KIF3A Microtubule plus end directed kinesin motor 3A Homo sapiens Human Arginine-glutamic acid dipeptide repeats protein Atrophin 1 like protein Atrophin 1 related protein Homo sapiens Human Cryptochrome-1 Homo sapiens Human Nuclear pore complex protein Nup153 Nucleoporin Nup153 153 kDa nucleoporin Homo sapiens Human Nuclear pore complex protein Nup153 Nucleoporin Nup153 153 kDa nucleoporin Homo sapiens Human Histone deacetylase 10 HD10Homo sapiens Human Actin-binding Rho activating protein Striated muscle activator of Rho dependent signaling STARS Homo sapiens Human Sterol regulatory element binding protein 1 SREBP1 Sterol regulatory element binding transcription factor 1 Homo sapiens Human Glial fibrillary acidic protein astrocyte GFAP Homo sapiens Human Caspase recruitment domain containing protein 14 CARD containing MAGUK protein 2 Carma 2 Homo sapiens Human Actin-binding Rho activating protein Striated muscle activator of Rho dependent signaling STARS Homo sapiens Human Nuclear pore complex protein Nup153 Nucleoporin Nup153 153 kDa nucleoporin Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human Zinc finger BED domain containing protein 4 Homo sapiens Human Protein phosphatase Slingshot homolog 2 EC 3 1 3 48 EC 3 1 3 16 SSH 2L hSSH 2L Homo sapiens Human Nuclear pore complex protein Nup153 Nucleoporin Nup153 153 kDa nucleoporin Homo sapiens Human Actin-binding Rho activating protein Striated muscle activator of Rho dependent signaling STARS Homo sapiens Human 185 552 683 590 512 593 175 639 136 553 946 243 558 909 491 520 366 377 309 576 393 669 535 206 1 2 3 4 49 19.47 698 50 51 18.67 18.41 52 53 18.33 18.15 54 17.45 55 16.76 56 16.60 57 58 16.52 16.13 59 16.06 60 61 16.05 15.67 62 63 15.48 15.43 64 65 66 67 15.38 15.23 15.13 14.75 68 69 14.62 14.57 70 14.32 71 14.23 72 14.18 DNA polymerase sigma EC 2 7 7 7 Topoisomerase related function protein 4 1 TRF4 1 LAK 1 DNA polymerase kappa Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human Nuclear pore complex protein Nup153 Nucleoporin Nup153 153 kDa nucleoporin Homo sapiens Human Uncharacterized protein C6orf60 Homo sapiens Human Nuclear pore complex protein Nup153 Nucleoporin Nup153 153 kDa nucleoporin Homo sapiens Human Actin-binding Rho activating protein Striated muscle activator of Rho dependent signaling STARS Homo sapiens Human Complex I intermediate associated protein 30 mitochondrial precursor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly factor 1 Homo sapiens Human Cadherin-like protein 26 precursor Cadherin like protein VR20 Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human Actin-binding Rho activating protein Striated muscle activator of Rho dependent signaling STARS Homo sapiens Human Calcium-transporting ATPase type 2C member 1 EC 3 6 3 8 ATPase 2C1 ATP dependent Ca 2 pump PMR1 Homo sapiens Human Bcl-2-modifying factor Homo sapiens Human Actin-binding Rho activating protein Striated muscle activator of Rho dependent signaling STARS Homo sapiens Human Bcl-2-modifying factor Homo sapiens Human Actin-binding Rho activating protein Striated muscle activator of Rho dependent signaling STARS Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human Uncharacterized protein C18orf54 precursor Homo sapiens Human Zinc finger protein 225 Homo sapiens Human Putative tyrosine protein phosphatase TPTE EC 3 1 3 48 Transmembrane phosphatase with tensin homology Protein BJ HCC 5 Homo sapiens Human Uncharacterized protein C6orf10 Homo sapiens Human Keratin, type I cytoskeletal 23 Cytokeratin 23 CK 23 Keratin 23 K23 Homo sapiens Human Neuronal PAS domain containing protein 1 Neuronal PAS1 Member of PAS protein 5 Basic helix loop helix PAS protein MOP5 Homo sapiens Human Complex I intermediate associated protein 30 mitochondrial precursor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly factor 1 Homo sapiens Human Nuclear pore complex protein Nup153 Nucleoporin Nup153 153 kDa nucleoporin Homo sapiens Human 403 469 134 375 829 888 508 923 594 186 710 589 567 700 860 707 544 600 184 170 261 235 675 207 1 2 3 4 73 14.09 704 74 14.08 75 76 77 13.99 13.96 13.66 78 79 13.24 13.16 80 13.16 81 13.13 82 83 13.06 12.89 84 12.80 85 12.73 86 12.71 87 12.60 88 12.47 89 12.44 90 12.39 91 92 11.91 11.85 93 94 95 11.80 11.74 11.73 Rho guanine nucleotide exchange factor 5 Guanine nucleotide regulatory protein TIM Oncogene TIM p60 TIM Transforming immortalized mammary oncogene Homo sapiens Human Sterol regulatory element binding protein 1 SREBP 1 Sterol regulatory element binding transcription factor 1 Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human Actin-binding Rho activating protein Striated muscle activator of Rho dependent signaling STARS Homo sapiens Human SAPS domain family member 2 Homo sapiens Human CAP-GLY domain containing linker protein 2 Cytoplasmic linker protein 2 Cytoplasmic linker protein 115 CLIP 115 Williams Beuren syndrome chromosome region 4 protein Homo sapiens Human CAP-GLY domain containing linker protein 2 Cytoplasmic linker protein 2 Cytoplasmic linker protein 115 CLIP 115 Williams Beuren syndrome chromosome region 4 protein Homo sapiens Human Fizzy-related protein homolog Fzr Cdh1 Hct1 homolog hCDH1 CDC20 like protein 1 Homo sapiens Human Bcl-2-modifying factor Homo sapiens Human DNA repair protein RAD50 EC 3 6 hRAD50 Homo sapiens Human Arginine-glutamic acid dipeptide repeats protein Atrophin 1 like protein Atrophin 1 related protein Homo sapiens Human Probable phospholipid transporting ATPase IF EC 3 6 3 1 ATPase class I type 11B ATPase IR Homo sapiens Human Nuclear pore complex protein Nup153 Nucleoporin Nup153 153 kDa nucleoporin Homo sapiens Human Nuclear pore complex protein Nup153 Nucleoporin Nup153 153 kDa nucleoporin Homo sapiens Human Cadherin-like protein 26 precursor Cadherin like protein VR20 Homo sapiens Human Rho guanine nucleotide exchange factor 5 Guanine nucleotide regulatory protein TIM Oncogene TIM p60 TIM Transforming immortalized mammary oncogene Homo sapiens Human Nuclear pore complex protein Nup153 Nucleoporin Nup153 153 kDa nucleoporin Homo sapiens Human Band 4 1 like protein 4A Protein NBL4 Homo sapiens Human Arginine-glutamic acid dipeptide repeats protein Atrophin 1 like protein Atrophin 1 related protein Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human Uncharacterized protein C18orf54 precursor Homo sapiens Human Ephrin type B receptor 6 precursor Tyrosine protein kinase defective receptor EPH 6 HEP Homo sapiens Human 503 836 892 703 264 271 271 220 478 487 622 395 679 943 904 279 514 213 823 852 575 161 208 1 2 96 11.67 Keratin-associated protein 21 2 Homo sapiens Human 3 427 4 97 11.67 Keratin-associated protein 21 2 Homo sapiens Human 427 98 11.65 668 99 100 11.59 11.54 101 11.51 102 11.34 103 11.33 104 11.28 105 11.25 106 107 108 11.21 11.19 11.05 109 11.03 110 10.76 111 10.72 112 10.71 113 10.66 114 10.63 115 10.44 116 10.44 117 10.35 118 10.23 Arginine-glutamic acid dipeptide repeats protein Atrophin 1 like protein Atrophin 1 related protein Homo sapiens Human Serine/threonine-protein Arginine-glutamic acid dipeptide repeats protein Atrophin 1 like protein Atrophin 1 related protein Homo sapiens Human Nuclear pore complex protein Nup153 Nucleoporin Nup153 153 kDa nucleoporin Homo sapiens Human Uncharacterized protein C18orf54 precursor Homo sapiens Human Protocadherin gamma A10 precursor PCDH gamma A10 Homo sapiens Human Nuclear pore complex protein Nup153 Nucleoporin Nup153 153 kDa nucleoporin Homo sapiens Human Zinc finger protein 143 SPH binding factor Homo sapiens Human Nucleolar protein 66 hsNO66 Homo sapiens Human Advillin p92 Homo sapiens Human Chondroitin sulfate glucuronyltransferase EC 2 4 1 226 N acetylgalactosaminyl proteoglycan 3 beta glucuronosyltransferase Chondroitin glucuronyltransferase II CSGlcA T Homo sapiens Human E3 ubiquitin protein ligase RNF19 EC 6 3 2 RING finger protein 19 Dorfin Double ring finger protein p38 protein Homo sapiens Human Ladinin 1 Lad 1 120 kDa linear IgA bullous dermatosis antigen 97 kDa linear IgA bullous dermatosis antigen Linear IgA disease antigen homolog LadA Homo sapiens Human Oligodendrocyte transcription factor 1 Oligo1 Homo sapiens Human Zinc finger BED domain containing protein 4 Homo sapiens Human Low-density lipoprotein receptor related protein 8 precursor Apolipoprotein E receptor 2 Homo sapiens Human Putative ATP dependent RNA helicase DHX33 EC 3 6 1 DEAH box protein 33 Homo sapiens Human Actin-binding Rho activating protein Striated muscle activator of Rho dependent signaling STARS Homo sapiens Human Actin-binding Rho activating protein Striated muscle activator of Rho dependent signaling STARS Homo sapiens Human Oligodendrocyte transcription factor 1 Oligo1 Homo sapiens Human Zinc finger BED domain containing protein 4 Homo sapiens Human 251 509 699 490 159 498 270 691 222 706 531 349 502 563 656 596 406 406 693 628 209 1 2 3 4 119 10.23 628 120 10.13 121 10.02 122 9.97 123 9.95 124 125 126 127 128 129 9.83 9.78 9.77 9.75 9.70 9.57 130 9.56 131 9.55 132 9.50 133 134 9.46 9.39 135 9.39 136 9.36 137 138 9.32 9.30 139 9.25 140 9.16 141 9.01 142 8.98 Zinc finger BED domain containing protein 4 Homo sapiens Human Probable G protein coupled receptor 158 precursor Homo sapiens Human G-protein-signaling modulator 1 Activator of G protein signaling 3 Homo sapiens Human Nuclear pore complex protein Nup153 Nucleoporin Nup153 153 kDa nucleoporin Homo sapiens Human Putative tyrosine protein phosphatase TPTE EC 3 1 3 48 Transmembrane phosphatase with tensin homology Protein BJ HCC 5 Homo sapiens Human Cryptochrome-1 Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human Solute Secretagogin Homo sapiens Human Mitochondrial intermediate peptidase mitochondrial precursor EC 3 4 24 59 MIP Homo sapiens Human Replication factor C subunit 2 Replication factor C 40 kDa subunit RF C 40 kDa subunit RFC40 Activator 1 40 kDa subunit A1 40 kDa subunit Homo sapiens Human Nuclear pore complex protein Nup153 Nucleoporin Nup153 153 kDa nucleoporin Homo sapiens Human Rho guanine nucleotide exchange factor 5 Guanine nucleotide regulatory protein TIM Oncogene TIM p60 TIM Transforming immortalized mammary oncogene Homo sapiens Human Uncharacterized protein C21orf62 B37 Homo sapiens Human G-protein-signaling modulator 1 Activator of G protein signaling 3 Homo sapiens Human G-protein-signaling modulator 1 Activator of G protein signaling 3 Homo sapiens Human G-protein-signaling modulator 1 Activator of G protein signaling 3 Homo sapiens Human Bcl-2-modifying factor Homo sapiens Human Complex I intermediate associated protein 30 mitochondrial precursor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly factor 1 Homo sapiens Human Nuclear pore complex protein Nup153 Nucleoporin Nup153 153 kDa nucleoporin Homo sapiens Human Oligodendrocyte transcription factor 1 Oligo1 Homo sapiens Human Complex I intermediate associated protein 30 mitochondrial precursor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly factor 1 Homo sapiens Human Nuclear pore complex protein Nup153 Nucleoporin Nup153 153 kDa nucleoporin Homo sapiens Human 191 585 621 591 110 853 861 361 320 564 219 486 290 472 614 614 259 556 437 369 664 118 385 210 1 2 3 4 143 8.76 139 144 145 146 8.73 8.67 8.62 147 148 8.59 8.54 149 150 151 152 8.53 8.50 8.50 8.45 153 154 155 8.44 8.44 8.41 156 157 8.31 8.22 158 8.21 159 8.21 160 8.20 161 8.15 162 8.14 163 8.14 164 8.09 165 166 8.05 8.04 167 8.02 168 169 7.97 7.92 Kinesin-like protein KIF3A Microtubule plus end directed kinesin motor 3A Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human Krueppel-like factor 15 Kidney enriched krueppel like factor Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human D-2-hydroxyglutarate dehydrogenase mitochondrial precursor EC 1 1 99 Homo sapiens Human Uncharacterized protein C20orf29 Homo sapiens Human Frizzled-2 precursor Fz 2 hFz2 FzE2 Homo sapiens Human Frizzled-2 precursor Fz 2 hFz2 FzE2 Homo sapiens Human Nuclear pore complex protein Nup153 Nucleoporin Nup153 153 kDa nucleoporin Homo sapiens Human Protein HFSE 1 Homo sapiens Human Protein HFSE 1 Homo sapiens Human Chondroitin sulfate glucuronyltransferase EC 2 4 1 226 N acetylgalactosaminyl proteoglycan 3 beta glucuronosyltransferase Chondroitin glucuronyltransferase II CSGlcA T Homo sapiens Human Bifunctional Nuclear pore complex protein Nup153 Nucleoporin Nup153 153 kDa nucleoporin Homo sapiens Human Zinc finger protein 250 Zinc finger protein 647 Homo sapiens Human Zinc finger protein 250 Zinc finger protein 647 Homo sapiens Human Arginine-glutamic acid dipeptide repeats protein Atrophin 1 like protein Atrophin 1 related protein Homo sapiens Human Rho guanine nucleotide exchange factor 5 Guanine nucleotide regulatory protein TIM Oncogene TIM p60 TIM Transforming immortalized mammary oncogene Homo sapiens Human Nuclear pore complex protein Nup153 Nucleoporin Nup153 153 kDa nucleoporin Homo sapiens Human Nuclear pore complex protein Nup153 Nucleoporin Nup153 153 kDa nucleoporin Homo sapiens Human Ladinin 1 Lad 1 120 kDa linear IgA bullous dermatosis antigen 97 kDa linear IgA bullous dermatosis antigen Linear IgA disease antigen homolog LadA Homo sapiens Human Uncharacterized protein C21orf62 B37 Homo sapiens Human Actin-binding Rho activating protein Striated muscle activator of Rho dependent signaling STARS Homo sapiens Human Zinc finger and BTB domain containing protein 41 Homo sapiens Human Collagen alpha 2 VI chain precursor Homo sapiens Human Uncharacterized protein C18orf54 precursor Homo sapiens Human 855 844 79 827 262 583 351 351 673 181 181 464 418 697 245 245 470 595 605 605 953 410 598 886 241 592 211 1 2 3 4 170 171 172 7.78 7.76 7.75 837 477 613 173 7.70 174 175 176 7.65 7.62 7.61 177 178 7.58 7.56 179 180 7.45 7.44 181 7.38 182 7.35 183 7.34 184 7.34 185 186 187 7.27 7.21 7.15 188 7.15 189 7.00 190 6.99 191 6.97 192 193 194 195 196 6.91 6.90 6.90 6.86 6.82 197 6.81 Keratin-associated protein 21 2 Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human Nuclear pore complex protein Nup153 Nucleoporin Nup153 153 kDa nucleoporin Homo sapiens Human Arginine-glutamic acid dipeptide repeats protein Atrophin 1 like protein Atrophin 1 related protein Homo sapiens Human Uncharacterized protein C21orf62 B37 Homo sapiens Human Uncharacterized protein C2orf21 Homo sapiens Human Arginine-glutamic acid dipeptide repeats protein Atrophin 1 like protein Atrophin 1 related protein Homo sapiens Human Bcl-2-modifying factor Homo sapiens Human Putative tyrosine protein phosphatase TPTE EC 3 1 3 48 Transmembrane phosphatase with tensin homology Protein BJ HCC 5 Homo sapiens Human PHD finger protein 8 Homo sapiens Human Arginine-glutamic acid dipeptide repeats protein Atrophin 1 like protein Atrophin 1 related protein Homo sapiens Human G-protein-signaling modulator 1 Activator of G protein signaling 3 Homo sapiens Human Cadherin-like protein 26 precursor Cadherin like protein VR20 Homo sapiens Human Nuclear pore complex protein Nup153 Nucleoporin Nup153 153 kDa nucleoporin Homo sapiens Human Nuclear pore complex protein Nup153 Nucleoporin Nup153 153 kDa nucleoporin Homo sapiens Human Secretagogin Homo sapiens Human Angiopoietin-1 precursor ANG 1 Homo sapiens Human Cadherin-like protein 26 precursor Cadherin like protein VR20 Homo sapiens Human Cadherin-like protein 26 precursor Cadherin like protein VR20 Homo sapiens Human Zinc finger and SCAN domain containing protein 4 Zinc finger protein 494 Homo sapiens Human Actin-binding Rho activating protein Striated muscle activator of Rho dependent signaling STARS Homo sapiens Human Oligodendrocyte transcription factor 1 Oligo1 Homo sapiens Human Dynamin-1-like Frizzled-2 precursor Fz 2 hFz2 FzE2 Homo sapiens Human Frizzled-2 precursor Fz 2 hFz2 FzE2 Homo sapiens Human Phosducin-like protein 2 Homo sapiens Human Actin-binding Rho activating protein Striated muscle activator of Rho dependent signaling STARS Homo sapiens Human Inositol polyphosphate multikinase EC 2 7 1 151 Inositol 1 3 4 6 tetrakisphosphate 5 kinase Homo sapiens Human 507 447 570 546 518 381 188 582 511 247 364 364 453 547 645 645 390 479 539 562 317 317 199 696 370 212 1 2 3 4 198 6.81 370 199 6.81 200 6.72 201 6.65 202 6.65 203 6.59 204 6.56 205 6.54 206 6.48 207 6.42 208 6.42 210 6.34 211 6.31 212 6.30 213 6.30 214 215 6.28 6.24 216 217 218 219 6.21 6.18 6.12 6.08 220 6.05 221 6.04 Inositol polyphosphate multikinase EC 2 7 1 151 Inositol 1 3 4 6 tetrakisphosphate 5 kinase Homo sapiens Human Inositol polyphosphate multikinase EC 2 7 1 151 Inositol 1 3 4 6 tetrakisphosphate 5 kinase Homo sapiens Human Uncharacterized protein C18orf54 precursor Homo sapiens Human Steroidogenic acute regulatory protein mitochondrial precursor StAR StARD1 Homo sapiens Human Steroidogenic acute regulatory protein mitochondrial precursor StAR StARD1 Homo sapiens Human Putative uncharacterized protein C10orf130 Homo sapiens Human Transcription factor AP 2 alpha AP2 alpha Activating enhancer binding protein 2 alpha AP 2 transcription factor Activator protein 2 AP 2 Homo sapiens Human Oligodendrocyte transcription factor 1 Oligo1 Homo sapiens Human Elongation factor G 1 mitochondrial precursor mEF G 1 Elongation factor G1 Homo sapiens Human Nuclear pore complex protein Nup153 Nucleoporin Nup153 153 kDa nucleoporin Homo sapiens Human Nuclear pore complex protein Nup153 Nucleoporin Nup153 153 kDa nucleoporin Homo sapiens Human Ubiquitin carboxyl terminal hydrolase 42 EC 3 1 2 15 Ubiquitin thioesterase 42 Ubiquitin specific processing protease 42 Deubiquitinating enzyme 42 Homo sapiens Human Hepatocyte nuclear factor 3 beta HNF 3B Forkhead box protein A2 Homo sapiens Human Mitochondrial intermediate peptidase mitochondrial precursor EC 3 4 24 59 MIP Homo sapiens Human Mitochondrial intermediate peptidase mitochondrial precursor EC 3 4 24 59 MIP Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human Low-density lipoprotein receptor related protein 8 precursor Apolipoprotein E receptor 2 Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human Transmembrane protein 106B Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human Regulator of nonsense transcripts 3A Nonsense mRNA reducing factor 3A Up frameshift suppressor 3 homolog A hUpf3 Homo sapiens Human Olfactory receptor 10A7 Olfactory receptor OR12 6 Homo sapiens Human Ladinin 1 Lad 1 120 kDa linear IgA bullous dermatosis antigen 97 kDa linear IgA bullous dermatosis antigen Linear IgA disease antigen homolog LadA Homo sapiens Human 370 497 445 445 543 640 612 560 391 391 501 870 348 348 454 662 905 357 430 610 165 638 213 1 2 3 4 222 223 5.96 5.86 215 263 224 225 5.81 5.80 226 227 228 5.78 5.77 5.73 229 230 5.72 5.68 231 232 233 234 5.60 5.53 5.53 5.52 235 236 237 238 239 5.51 5.49 5.46 5.46 5.44 240 241 5.37 5.30 242 243 244 245 5.29 5.29 5.27 5.26 246 247 248 249 5.20 5.20 5.15 5.12 250 5.11 251 252 253 254 5.10 5.09 5.09 5.06 Keratin-associated protein 21 2 Homo sapiens Human Spartin Trans activated by hepatitis C virus core protein 1 Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human Oligodendrocyte transcription factor 1 Oligo1 Homo sapiens Human Secretagogin Homo sapiens Human Nucleolar protein 66 hsNO66 Homo sapiens Human G-protein-signaling modulator 1 Activator of G protein signaling 3 Homo sapiens Human Transmembrane protein 106B Homo sapiens Human Oligodendrocyte transcription factor 1 Oligo1 Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human Nuclear pore complex protein Nup153 Nucleoporin Nup153 153 kDa nucleoporin Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human Protein Wnt 8a precursor Wnt 8d Homo sapiens Human Cryptochrome-1 Homo sapiens Human Cryptochrome-1 Homo sapiens Human Arginine-glutamic acid dipeptide repeats protein Atrophin 1 like protein Atrophin 1 related protein Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human Arginine-glutamic acid dipeptide repeats protein Atrophin 1 like protein Atrophin 1 related protein Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human Uncharacterized protein C21orf62 B37 Homo sapiens Human Olfactory receptor 10A7 Olfactory receptor OR12 6 Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human Histone deacetylase 10 HD10 Homo sapiens Human Sterol regulatory element binding protein 1 SREBP 1 Sterol regulatory element binding transcription factor 1 Homo sapiens Human Brain-specific angiogenesis inhibitor 1 precursor Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human Calcium-transporting ATPase type 2C member 1 EC 3 6 3 8 ATPase 2C1 ATP dependent Ca 2 pump PMR1 Homo sapiens Human 316 945 300 601 967 919 319 890 297 297 580 426 677 254 254 537 534 876 840 840 468 432 433 433 355 678 413 428 329 329 147 214 1 2 3 4 255 5.02 500 256 5.00 257 258 4.99 4.98 259 4.96 260 4.96 261 4.91 262 263 4.90 4.86 264 4.80 265 4.80 266 4.76 267 4.75 268 4.74 269 270 271 272 4.72 4.72 4.72 4.70 273 4.68 274 4.67 275 4.65 Oligodendrocyte transcription factor 1 Oligo1 Homo sapiens Human Nuclear pore complex protein Nup153 Nucleoporin Nup153 153 kDa nucleoporin Homo sapiens Human ORM1-like protein 3 Homo sapiens Human Ladinin 1 Lad 1 120 kDa linear IgA bullous dermatosis antigen 97 kDa linear IgA bullous dermatosis antigen Linear IgA disease antigen homolog LadA Homo sapiens Human Complex I intermediate associated protein 30 mitochondrial precursor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly factor 1 Homo sapiens Human Complex I intermediate associated protein 30 mitochondrial precursor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly factor 1 Homo sapiens Human Olfactory receptor 10A7 Olfactory receptor OR12 6 Homo sapiens Human MARVEL domain containing protein 1 Homo sapiens Human E3 ubiquitin protein ligase RNF19 EC 6 3 2 RING finger protein 19 Dorfin Double ring finger protein p38 protein Homo sapiens Human Nuclear pore complex protein Nup153 Nucleoporin Nup153 153 kDa nucleoporin Homo sapiens Human Nuclear pore complex protein Nup153 Nucleoporin Nup153 153 kDa nucleoporin Homo sapiens Human Nuclear pore complex protein Nup153 Nucleoporin Nup153 153 kDa nucleoporin Homo sapiens Human Hematopoietic progenitor cell antigen CD34 precursor Homo sapiens Human Ubiquitin carboxyl terminal hydrolase 16 EC 3 1 2 15 Ubiquitin thioesterase 16 Ubiquitin specific processing protease 16 Deubiquitinating enzyme 16 Ubiquitin processing protease UBP M Homo sapiens Human Transmembrane protein 106B Homo sapiens Human Transmembrane protein 106B Homo sapiens Human Transmembrane protein 106B Homo sapiens Human Zinc finger BED domain containing protein 4 Homo sapiens Human Antigen peptide transporter 2 APT2 ATP binding cassette sub family B member 3 Peptide transporter TAP2 Peptide transporter PSF2 Peptide supply factor 2 PSF 2 Peptide transporter involved in antigen processing 2 Homo sapiens Human Putative tyrosine protein phosphatase TPTE EC 3 1 3 48 Transmembrane phosphatase with tensin homology Protein BJ HCC 5 Homo sapiens Human cAMP-dependent protein kinase inhibitor alpha PKI alpha cAMP dependent protein kinase inhibitor muscle brain isoform Homo sapiens Human 688 373 525 280 280 834 380 274 597 597 538 914 629 289 289 289 636 572 928 153 215 1 2 3 4 276 4.65 153 277 4.63 278 4.61 279 4.60 280 4.60 281 4.58 282 4.54 283 284 4.52 4.50 285 286 287 288 4.49 4.48 4.48 4.46 289 4.44 290 291 4.43 4.41 292 4.41 293 4.41 294 295 4.35 4.34 296 297 298 4.33 4.33 4.32 299 4.32 cAMP-dependent protein kinase inhibitor alpha PKI alpha cAMP dependent protein kinase inhibitor muscle brain isoform Homo sapiens Human Probable palmitoyltransferase ZDHHC4 EC 2 3 1 Zinc finger DHHC domain containing protein 4 DHHC 4 Zinc finger protein 374 Homo sapiens Human Telomeric repeat binding factor 2 TTAGGG repeat binding factor 2 Telomeric DNA binding protein Homo sapiens Human Reticulon-2 Neuroendocrine specific protein like 1 NSP like protein 1 NSPLI Homo sapiens Human Reticulon-2 Neuroendocrine specific protein like 1 NSP like protein 1 NSPLI Homo sapiens Human Complex I intermediate associated protein 30 mitochondrial precursor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly factor 1 Homo sapiens Human Probable phospholipid transporting ATPase IC EC 3 6 3 1 Familial intrahepatic cholestasis type 1 ATPase class I type 8B member 1 Homo sapiens Human Transmembrane protein 106B Homo sapiens Human Ladinin 1 Lad 1 120 kDa linear IgA bullous dermatosis antigen 97 kDa linear IgA bullous dermatosis antigen Linear IgA disease antigen homolog LadA Homo sapiens Human UPF0407 protein C2orf39 Homo sapiens Human Uncharacterized protein C6orf10 Homo sapiens Human Uncharacterized protein C6orf10 Homo sapiens Human Arginine-glutamic acid dipeptide repeats protein Atrophin 1 like protein Atrophin 1 related protein Homo sapiens Human Zinc finger and BTB domain containing protein 26 Zinc finger protein 481 Zinc finger protein Bioref Homo sapiens Human L-myc-1 proto oncogene protein Homo sapiens Human Nuclear pore complex protein Nup153 Nucleoporin Nup153 153 kDa nucleoporin Homo sapiens Human Nuclear pore complex protein Nup153 Nucleoporin Nup153 153 kDa nucleoporin Homo sapiens Human Nuclear pore complex protein Nup153 Nucleoporin Nup153 153 kDa nucleoporin Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human G-protein-signaling modulator 1 Activator of G protein signaling 3 Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human Arginine-glutamic acid dipeptide repeats protein Atrophin 1 like protein Atrophin 1 related protein Homo sapiens Human Arginine-glutamic acid dipeptide repeats protein Atrophin 1 like protein Atrophin 1 related protein Homo sapiens Human 542 388 295 295 626 882 223 272 452 269 269 365 485 527 298 298 298 420 960 307 307 360 360 216 1 2 3 4 300 4.31 359 301 4.25 302 303 4.24 4.23 304 305 4.17 4.13 306 4.13 307 308 309 310 4.12 4.12 4.12 4.08 311 4.07 312 4.07 313 4.07 314 4.01 315 4.00 316 3.97 317 3.95 318 3.94 319 3.92 320 3.91 Complex I intermediate associated protein 30 mitochondrial precursor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly factor 1 Homo sapiens Human E3 ubiquitin protein ligase RNF19 EC 6 3 2 RING finger protein 19 Dorfin Double ring finger protein p38 protein Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human Kinesin-like protein KIF3A Microtubule plus end directed kinesin motor 3A Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human Cadherin-like protein 26 precursor Cadherin like protein VR20 Homo sapiens Human Cadherin-like protein 26 precursor Cadherin like protein VR20 Homo sapiens Human Uncharacterized protein C12orf5 Homo sapiens Human Uncharacterized protein C12orf5 Homo sapiens Human Uncharacterized protein C12orf5 Homo sapiens Human Ladinin 1 Lad 1 120 kDa linear IgA bullous dermatosis antigen 97 kDa linear IgA bullous dermatosis antigen Linear IgA disease antigen homolog LadA Homo sapiens Human Complex I intermediate associated protein 30 mitochondrial precursor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly factor 1 Homo sapiens Human Complex I intermediate associated protein 30 mitochondrial precursor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly factor 1 Homo sapiens Human Complex I intermediate associated protein 30 mitochondrial precursor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly factor 1 Homo sapiens Human Olfactory receptor 10A7 Olfactory receptor OR12 6 Homo sapiens Human DNA-directed RNA polymerase I 135 kDa polypeptide EC 2 7 7 6 RNA polymerase I subunit 2 RPA135 Homo sapiens Human Trefoil factor 3 precursor Intestinal trefoil factor hP1 B Homo sapiens Human Ladinin 1 Lad 1 120 kDa linear IgA bullous dermatosis antigen 97 kDa linear IgA bullous dermatosis antigen Linear IgA disease antigen homolog LadA Homo sapiens Human Regenerating islet derived protein 4 precursor Reg IV REG like protein Gastrointestinal secretory protein Homo sapiens Human Complex I intermediate associated protein 30 mitochondrial precursor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly factor 1 Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human 338 523 244 897 278 278 180 180 180 386 441 441 441 644 505 833 657 847 924 459 217 1 2 3 4 321 3.90 313 322 3.88 323 3.82 324 3.81 325 3.80 326 3.79 327 328 329 330 3.77 3.76 3.76 3.73 331 3.71 332 3.66 333 3.65 334 335 3.63 3.61 336 3.61 337 338 3.60 3.59 339 340 341 3.55 3.54 3.53 Chondroitin sulfate glucuronyltransferase EC 2 4 1 226 N acetylgalactosaminyl proteoglycan 3 beta glucuronosyltransferase Chondroitin glucuronyltransferase II CSGlcA T Homo sapiens Human Reticulon-2 Neuroendocrine specific protein like 1 NSP like protein 1 NSPLI Homo sapiens Human Kinesin-like protein KIF3A Microtubule plus end directed kinesin motor 3A Homo sapiens Human Ladinin 1 Lad 1 120 kDa linear IgA bullous dermatosis antigen 97 kDa linear IgA bullous dermatosis antigen Linear IgA disease antigen homolog LadA Homo sapiens Human Calcium-transporting ATPase type 2C member 1 EC 3 6 3 8 ATPase 2C1 ATP dependent Ca 2 pump PMR1 Homo sapiens Human Ladinin 1 Lad 1 120 kDa linear IgA bullous dermatosis antigen 97 kDa linear IgA bullous dermatosis antigen Linear IgA disease antigen homolog LadA Homo sapiens Human NEDD4-binding protein 3 N4BP3 Homo sapiens Human Zinc finger protein 691 Homo sapiens Human Zinc finger protein 691 Homo sapiens Human Ladinin 1 Lad 1 120 kDa linear IgA bullous dermatosis antigen 97 kDa linear IgA bullous dermatosis antigen Linear IgA disease antigen homolog LadA Homo sapiens Human Ladinin 1 Lad 1 120 kDa linear IgA bullous dermatosis antigen 97 kDa linear IgA bullous dermatosis antigen Linear IgA disease antigen homolog LadA Homo sapiens Human Regulator of G protein signaling 22 RGS22 Homo sapiens Human Probable phospholipid transporting ATPase IF EC 3 6 3 1 ATPase class I type 11B ATPase IR Homo sapiens Human Transmembrane protein 106B Homo sapiens Human Complex I intermediate associated protein 30 mitochondrial precursor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly factor 1 Homo sapiens Human Complex I intermediate associated protein 30 mitochondrial precursor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly factor 1 Homo sapiens Human Frizzled-2 precursor Fz 2 hFz2 FzE2 Homo sapiens Human Nuclear pore complex protein Nup153 Nucleoporin Nup153 153 kDa nucleoporin Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human Frizzled-2 precursor Fz 2 hFz2 FzE2 Homo sapiens Human Suppressor of cytokine signaling 6 SOCS 6 Suppressor of cytokine signaling 4 SOCS 4 Cytokine inducible SH2 protein 4 CIS 4 Homo sapiens Human 545 917 451 200 631 276 462 462 510 483 207 494 889 824 824 399 488 457 398 378 218 1 2 3 4 342 3.53 378 343 3.52 344 3.51 345 3.46 346 3.45 347 3.45 348 349 3.44 3.40 350 3.39 351 3.38 352 3.36 353 3.35 354 3.33 355 3.30 356 3.30 357 3.28 358 3.26 359 3.26 360 3.25 Suppressor of cytokine signaling 6 SOCS 6 Suppressor of cytokine signaling 4 SOCS 4 Cytokine inducible SH2 protein 4 CIS 4 Homo sapiens Human Regenerating islet derived protein 4 precursor Reg IV REG like protein Gastrointestinal secretory protein Homo sapiens Human Hexokinase-3 EC 2 7 1 1 Hexokinase type III HK III Homo sapiens Human Arginine-glutamic acid dipeptide repeats protein Atrophin 1 like protein Atrophin 1 related protein Homo sapiens Human Oligodendrocyte transcription factor 1 Oligo1 Homo sapiens Human Oligodendrocyte transcription factor 1 Oligo1 Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human ER degradation enhancing alpha mannosidase like 1 Homo sapiens Human Complex I intermediate associated protein 30 mitochondrial precursor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly factor 1 Homo sapiens Human Zinc finger protein 143 SPH binding factor Homo sapiens Human Nuclear pore complex protein Nup98 Nup96 precursor Contains Nuclear pore complex protein Nup98 Nucleoporin Nup98 98 kDa nucleoporin Nuclear pore complex protein Nup96 Nucleoporin Nup96 96 kDa nucleoporin Homo sapiens Human Olfactory receptor 10A7 Olfactory receptor OR12 6 Homo sapiens Human Regenerating islet derived protein 4 precursor Reg IV REG like protein Gastrointestinal secretory protein Homo sapiens Human Probable phospholipid transporting ATPase ID EC 3 6 3 1 ATPase class I type 8B member 2 Homo sapiens Human Probable phospholipid transporting ATPase ID EC 3 6 3 1 ATPase class I type 8B member 2 Homo sapiens Human DNA topoisomerase 2 binding protein 1 DNA topoisomerase II binding protein 1 DNA topoisomerase IIbeta binding protein 1 TopBP1 Homo sapiens Human PH domain leucine rich repeat protein phosphatase like EC 3 1 3 16 Homo sapiens Human PH domain leucine rich repeat protein phosphatase like EC 3 1 3 16 Homo sapiens Human Complex I intermediate associated protein 30 mitochondrial precursor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly factor 1 Homo sapiens Human 828 651 825 526 526 440 599 619 256 333 205 637 202 202 513 284 284 666 219 1 2 3 4 361 3.25 666 362 363 3.23 3.19 364 3.16 365 3.16 366 3.15 367 3.15 368 3.14 369 3.10 370 3.10 371 3.08 372 3.08 373 3.06 374 3.06 375 3.03 376 377 378 3.02 3.02 3.01 379 2.99 380 381 382 2.98 2.98 2.98 Complex I intermediate associated protein 30 mitochondrial precursor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly factor 1 Homo sapiens Human Zinc finger protein 225 Homo sapiens Human Nuclear pore complex protein Nup153 Nucleoporin Nup153 153 kDa nucleoporin Homo sapiens Human Oligodendrocyte transcription factor 1 Oligo1 Homo sapiens Human Oligodendrocyte transcription factor 1 Oligo1 Homo sapiens Human COUP transcription factor 2 COUP TF2 COUP TF II Apolipoprotein AI regulatory protein 1 ARP 1 Homo sapiens Human COUP transcription factor 2 COUP TF2 COUP TF II Apolipoprotein AI regulatory protein 1 ARP 1 Homo sapiens Human Beta-mannosidase precursor EC 3 2 1 25 Lysosomal beta A mannosidase Mannanase Mannase Homo sapiens Human Complex I intermediate associated protein 30 mitochondrial precursor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly factor 1 Homo sapiens Human Complex I intermediate associated protein 30 mitochondrial precursor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly factor 1 Homo sapiens Human Regenerating islet derived protein 4 precursor Reg IV REG like protein Gastrointestinal secretory protein Homo sapiens Human Regenerating islet derived protein 4 precursor Reg IV REG like protein Gastrointestinal secretory protein Homo sapiens Human Nuclear pore complex protein Nup153 Nucleoporin Nup153 153 kDa nucleoporin Homo sapiens Human Nuclear pore complex protein Nup153 Nucleoporin Nup153 153 kDa nucleoporin Homo sapiens Human SH3 protein expressed in lymphocytes homolog Homo sapiens Human Frizzled-2 precursor Fz 2 hFz2 FzE2 Homo sapiens Human Frizzled-2 precursor Fz 2 hFz2 FzE2 Homo sapiens Human Arginine-glutamic acid dipeptide repeats protein Atrophin 1 like protein Atrophin 1 related protein Homo sapiens Human Ladinin 1 Lad 1 120 kDa linear IgA bullous dermatosis antigen 97 kDa linear IgA bullous dermatosis antigen Linear IgA disease antigen homolog LadA Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human 236 489 356 356 182 182 940 649 649 414 414 392 392 408 285 285 415 475 436 436 436 220 1 2 383 2.98 Keratin-associated protein 21 2 Homo sapiens Human 3 436 4 384 2.94 694 385 2.88 386 2.88 387 2.87 388 2.86 389 2.86 390 2.86 391 392 2.85 2.84 393 2.83 Oligodendrocyte transcription factor 1 Oligo1 Homo sapiens Human Zinc finger protein 295 Zinc finger and BTB domain containing protein 21 Homo sapiens Human Zinc finger protein 295 Zinc finger and BTB domain containing protein 21 Homo sapiens Human Zinc finger protein 295 Zinc finger and BTB domain containing protein 21 Homo sapiens Human LIM domain transcription factor LMO4 LIM domain only protein 4 LMO 4 Breast tumor autoantigen Homo sapiens Human LIM domain transcription factor LMO4 LIM domain only protein 4 LMO 4 Breast tumor autoantigen Homo sapiens Human LIM domain transcription factor LMO4 LIM domain only protein 4 LMO 4 Breast tumor autoantigen Homo sapiens Human Profilin-3 Profilin III Homo sapiens Human Late cornified envelope protein 3C Late envelope protein 15 Small proline rich like epidermal differentiation complex protein 3A Homo sapiens Human Zinc finger protein 560 Homo sapiens Human 394 2.83 Zinc finger protein 560 Homo sapiens Human 466 395 2.82 402 396 2.82 397 2.81 398 2.77 399 2.76 400 2.76 401 2.75 402 2.75 403 2.74 Treacle protein Treacher Collins syndrome protein Homo sapiens Human Treacle protein Treacher Collins syndrome protein Homo sapiens Human Cullin-associated NEDD8 dissociated protein 2 Cullin associated and neddylation dissociated protein 2 p120 CAND2 Homo sapiens Human Zinc finger protein 295 Zinc finger and BTB domain containing protein 21 Homo sapiens Human Complex I intermediate associated protein 30 mitochondrial precursor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly factor 1 Homo sapiens Human Complex I intermediate associated protein 30 mitochondrial precursor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly factor 1 Homo sapiens Human Methionyl-tRNA synthetase cytoplasmic EC 6 1 1 10 Methionine tRNA ligase MetRS Homo sapiens Human Methionyl-tRNA synthetase cytoplasmic EC 6 1 1 10 Methionine tRNA ligase MetRS Homo sapiens Human Protein yippee like 4 Homo sapiens Human 273 273 571 132 132 132 315 891 466 402 586 559 211 211 660 660 294 221 1 2 3 4 404 2.73 826 405 2.71 406 2.70 407 2.69 408 2.69 409 2.68 410 2.68 411 2.67 412 2.66 413 2.63 414 2.63 415 2.62 416 2.62 417 2.62 418 2.61 419 2.60 Regenerating islet derived protein 4 precursor Reg IV REG like protein Gastrointestinal secretory protein Homo sapiens Human Hemoglobin subunit gamma 1 Hemoglobin gamma 1 chain Gamma 1 globin Hemoglobin gamma A chain Hb F Agamma Homo sapiens Human G-protein-signaling modulator 1 Activator of G protein signaling 3 Homo sapiens Human Chondroitin sulfate glucuronyltransferase EC 2 4 1 226 N acetylgalactosaminyl proteoglycan 3 beta glucuronosyltransferase Chondroitin glucuronyltransferase II CSGlcA T Homo sapiens Human Chondroitin sulfate glucuronyltransferase EC 2 4 1 226 N acetylgalactosaminyl proteoglycan 3 beta glucuronosyltransferase Chondroitin glucuronyltransferase II CSGlcA T Homo sapiens Human Regenerating islet derived protein 4 precursor Reg IV REG like protein Gastrointestinal secretory protein Homo sapiens Human Regenerating islet derived protein 4 precursor Reg IV REG like protein Gastrointestinal secretory protein Homo sapiens Human Regenerating islet derived protein 4 precursor Reg IV REG like protein Gastrointestinal secretory protein Homo sapiens Human Complex I intermediate associated protein 30 mitochondrial precursor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly factor 1 Homo sapiens Human Regenerating islet derived protein 4 precursor Reg IV REG like protein Gastrointestinal secretory protein Homo sapiens Human Regenerating islet derived protein 4 precursor Reg IV REG like protein Gastrointestinal secretory protein Homo sapiens Human Interleukin-18 receptor 1 precursor IL1 receptor related protein IL 1Rrp CD218a antigen CDw218a Homo sapiens Human Interleukin-18 receptor 1 precursor IL1 receptor related protein IL 1Rrp CD218a antigen CDw218a Homo sapiens Human Interleukin-18 receptor 1 precursor IL1 receptor related protein IL 1Rrp CD218a antigen CDw218a Homo sapiens Human Ladinin 1 Lad 1 120 kDa linear IgA bullous dermatosis antigen 97 kDa linear IgA bullous dermatosis antigen Linear IgA disease antigen homolog LadA Homo sapiens Human Actin-binding Rho activating protein Striated muscle activator of Rho dependent signaling STARS Homo sapiens Human 208 961 383 383 609 609 653 281 634 634 178 178 178 529 654 222 1 2 3 4 420 2.60 654 421 2.59 422 2.59 423 2.58 424 2.55 425 2.54 426 2.53 427 2.52 428 2.52 429 2.52 430 2.51 431 2.51 432 433 434 435 436 437 2.50 2.49 2.48 2.47 2.47 2.46 438 2.46 439 2.45 440 2.43 Actin-binding Rho activating protein Striated muscle activator of Rho dependent signaling STARS Homo sapiens Human Complex I intermediate associated protein 30 mitochondrial precursor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly factor 1 Homo sapiens Human Complex I intermediate associated protein 30 mitochondrial precursor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly factor 1 Homo sapiens Human Regenerating islet derived protein 4 precursor Reg IV REG like protein Gastrointestinal secretory protein Homo sapiens Human Tubulin-specific chaperone cofactor E like protein EL Leucine rich repeat containing protein 35 Homo sapiens Human Heat-shock protein beta 3 HspB3 Heat shock 17 kDa protein Homo sapiens Human Zinc finger MYM type protein 3 Zinc finger protein 261 Homo sapiens Human Ladinin 1 Lad 1 120 kDa linear IgA bullous dermatosis antigen 97 kDa linear IgA bullous dermatosis antigen Linear IgA disease antigen homolog LadA Homo sapiens Human Ladinin 1 Lad 1 120 kDa linear IgA bullous dermatosis antigen 97 kDa linear IgA bullous dermatosis antigen Linear IgA disease antigen homolog LadA Homo sapiens Human Ladinin 1 Lad 1 120 kDa linear IgA bullous dermatosis antigen 97 kDa linear IgA bullous dermatosis antigen Linear IgA disease antigen homolog LadA Homo sapiens Human Late cornified envelope protein 3C Late envelope protein 15 Small proline rich like epidermal differentiation complex protein 3A Homo sapiens Human Late cornified envelope protein 3C Late envelope protein 15 Small proline rich like epidermal differentiation complex protein 3A Homo sapiens Human Protein yippee like 4 Homo sapiens Human Collagen alpha 1 XVI chain precursor Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human Band 4 1 like protein 4A Protein NBL4 Homo sapiens Human Band 4 1 like protein 4A Protein NBL4 Homo sapiens Human Complex I intermediate associated protein 30 mitochondrial precursor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly factor 1 Homo sapiens Human Complex I intermediate associated protein 30 mitochondrial precursor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly factor 1 Homo sapiens Human Olfactory receptor 10A7 Olfactory receptor OR12 6 Homo sapiens Human Zinc finger protein 250 Zinc finger protein 647 Homo sapiens Human 555 555 407 193 968 857 471 471 471 620 620 277 431 894 423 423 305 305 350 382 223 1 2 3 4 441 442 2.42 2.40 618 367 443 2.40 444 445 446 447 2.37 2.34 2.31 2.30 448 2.30 449 2.29 Transmembrane protein 106B Homo sapiens Human Complex I intermediate associated protein 30 mitochondrial precursor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly factor 1 Homo sapiens Human Complex I intermediate associated protein 30 mitochondrial precursor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly factor 1 Homo sapiens Human Syntaphilin Homo sapiens Human Calpain-5 EC 3 4 22 nCL 3 htra 3 Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human Neuropeptide B precursor Preproprotein L7 hPPL7 Contains Neuropeptide B 23 NPB23 hL7 Neuropeptide B 29 NPB29 hL7C Homo sapiens Human Neuropeptide B precursor Preproprotein L7 hPPL7 Contains Neuropeptide B 23 NPB23 hL7 Neuropeptide B 29 NPB29 hL7C Homo sapiens Human Protein yippee like 4 Homo sapiens Human 450 2.27 451 367 670 242 463 384 384 311 633 2.23 Arginine-glutamic acid dipeptide repeats protein Atrophin 1 like protein Atrophin 1 related protein Homo sapiens Human Band 4 1 like protein 4A Protein NBL4 Homo sapiens Human 452 2.22 Keratin-associated protein 21 2 Homo sapiens Human 435 453 2.19 303 454 2.19 455 2.16 456 2.15 457 2.12 458 2.11 459 2.11 460 2.11 461 2.10 462 2.10 463 2.08 Olfactory receptor 10A7 Olfactory receptor OR12 6 Homo sapiens Human Olfactory receptor 10A7 Olfactory receptor OR12 6 Homo sapiens Human Oligodendrocyte transcription factor 1 Oligo1 Homo sapiens Human ER degradation enhancing alpha mannosidase like 1 Homo sapiens Human Complex I intermediate associated protein 30 mitochondrial precursor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly factor 1 Homo sapiens Human PHD finger protein 21A BRAF35 HDAC complex protein BHC80 BHC80a Homo sapiens Human PHD finger protein 21A BRAF35 HDAC complex protein BHC80 BHC80a Homo sapiens Human PHD finger protein 21A BRAF35 HDAC complex protein BHC80 BHC80a Homo sapiens Human Zinc finger protein 295 Zinc finger and BTB domain containing protein 21 Homo sapiens Human Zinc finger protein 295 Zinc finger and BTB domain containing protein 21 Homo sapiens Human Ladinin 1 Lad 1 120 kDa linear IgA bullous dermatosis antigen 97 kDa linear IgA bullous dermatosis antigen Linear IgA disease antigen homolog LadA Homo sapiens Human 926 303 275 372 296 325 325 325 409 409 299 224 1 2 464 2.08 465 2.08 466 467 2.06 2.05 468 2.02 469 2.01 470 471 2.00 1.98 472 1.96 473 1.95 474 1.94 3 Ladinin 1 Lad 1 120 kDa linear IgA bullous dermatosis antigen 97 kDa linear IgA bullous dermatosis antigen Linear IgA disease antigen homolog LadA Homo sapiens Human Ladinin 1 Lad 1 120 kDa linear IgA bullous dermatosis antigen 97 kDa linear IgA bullous dermatosis antigen Linear IgA disease antigen homolog LadA Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human BAX protein cytoplasmic isoform gamma Homo sapiens Human Glutaryl-CoA dehydrogenase mitochondrial precursor EC 1 3 99 7 GCD Homo sapiens Human Olfactory receptor 10A7 Olfactory receptor OR12 6 Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human Serine/threonine-protein kinase Pim 3 EC 2 7 11 1 Homo sapiens Human Oligodendrocyte transcription factor 1 Oligo1 Homo sapiens Human Uncharacterized protein C18orf54 precursor Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human 4 299 299 446 324 550 971 421 659 460 687 190 475 1.94 Keratin-associated protein 21 2 Homo sapiens Human 190 476 1.93 839 477 1.92 478 1.92 479 1.91 Adenylate cyclase type 9 EC 4 6 1 1 Adenylate cyclase type IX ATP pyrophosphate lyase 9 Adenylyl cyclase 9 Homo sapiens Human Glutaryl-CoA dehydrogenase mitochondrial precursor EC 1 3 99 7 GCD Homo sapiens Human Glutaryl-CoA dehydrogenase mitochondrial precursor EC 1 3 99 7 GCD Homo sapiens Human Melanocortin receptor 5 MC5 R MC 2 Homo sapiens Human 480 1.91 Melanocortin receptor 5 MC5 R MC 2 Homo sapiens Human 214 481 1.89 Transmembrane protein 106B Homo sapiens Human 533 482 1.88 540 483 484 485 1.87 1.87 1.84 486 1.82 Integrin-linked protein kinase EC 2 7 11 1 ILK 1 ILK 2 59 kDa serine threonine protein kinase p59ILK Homo sapiens Human Protein yippee like 4 Homo sapiens Human Protein yippee like 4 Homo sapiens Human Ladinin 1 Lad 1 120 kDa linear IgA bullous dermatosis antigen 97 kDa linear IgA bullous dermatosis antigen Linear IgA disease antigen homolog LadA Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human 419 487 1.82 Keratin-associated protein 21 2 Homo sapiens Human 419 488 1.82 Keratin-associated protein 21 2 Homo sapiens Human 419 354 354 214 293 293 663 225 1 2 489 1.81 3 4 Regulator of differentiation 1 Rod1 Homo sapiens Human 258 400 490 1.80 PHD finger protein 8 Homo sapiens Human 491 1.79 Transmembrane protein 106B Homo sapiens Human 346 492 1.76 Cadherin-like protein 26 precursor Cadherin like protein VR20 Homo sapiens Human 260 493 1.75 671 494 1.74 495 1.73 496 1.72 497 1.72 498 1.72 499 1.68 Reticulon-2 Neuroendocrine specific protein like 1 NSP like protein 1 NSPLI Homo sapiens Human MAM domain containing protein 2 precursor Homo sapiens Human Complex I intermediate associated protein 30 mitochondrial precursor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly factor 1 Homo sapiens Human Calcium-transporting ATPase type 2C member 1 EC 3 6 3 8 ATPase 2C1 ATP dependent Ca 2 pump PMR1 Homo sapiens Human Calcium-transporting ATPase type 2C member 1 EC 3 6 3 8 ATPase 2C1 ATP dependent Ca 2 pump PMR1 Homo sapiens Human Calcium-transporting ATPase type 2C member 1 EC 3 6 3 8 ATPase 2C1 ATP dependent Ca 2 pump PMR1 Homo sapiens Human Peroxisome 500 1.67 501 1.67 502 1.64 503 1.62 504 1.62 505 1.60 506 1.58 Olfactory receptor 10A7 Olfactory receptor OR12 6 Homo sapiens Human Olfactory receptor 10A7 Olfactory receptor OR12 6 Homo sapiens Human Regenerating islet derived protein 4 precursor Reg IV REG like protein Gastrointestinal secretory protein Homo sapiens Human Regulator of G protein signaling 22 RGS22 Homo sapiens Human Regulator of G protein signaling 22 RGS22 Homo sapiens Human Inositol polyphosphate multikinase EC 2 7 1 151 Inositol 1 3 4 6 tetrakisphosphate 5 kinase Homo sapiens Human Transmembrane protein 106B Homo sapiens Human 507 1.58 Transmembrane protein 106B Homo sapiens Human 508 1.58 Transmembrane protein 106B Homo sapiens Human 143 509 1.56 Cullin-4B CUL 4B Homo sapiens Human 458 854 900 158 158 158 376 283 283 541 248 248 310 143 143 510 1.56 Cullin-4B CUL 4B Homo sapiens Human 458 511 1.54 Ankyrin repeat family A protein 2 RFXANK like 2 Homo sapiens Human 166 226 1 2 3 4 512 1.52 116 513 1.52 514 1.49 515 1.44 516 1.41 517 1.40 518 1.40 519 1.40 520 1.39 521 1.38 522 1.38 523 1.37 524 1.35 525 526 1.31 1.30 527 1.29 528 1.28 529 1.28 E3 ubiquitin protein ligase MIB2 EC 6 3 2 Mind bomb homolog 2 Zinc finger ZZ type with ankyrin repeat domain protein 1 Skeletrophin Novelzin Novel zinc finger protein Putative NF kappa B activating protein 002N Homo sapiens Human E3 ubiquitin protein ligase MIB2 EC 6 3 2 Mind bomb homolog 2 Zinc finger ZZ type with ankyrin repeat domain protein 1 Skeletrophin Novelzin Novel zinc finger protein Putative NF kappa B activating protein 002N Homo sapiens Human Coiled-coil domain containing protein 85A Homo sapiens Human Olfactory receptor 10A7 Olfactory receptor OR12 6 Homo sapiens Human Ubiquitin carboxyl terminal hydrolase 13 EC 3 1 2 15 Ubiquitin thioesterase 13 Ubiquitin specific processing protease 13 Deubiquitinating enzyme 13 Isopeptidase T 3 ISOT 3 Homo sapiens Human Trefoil factor 3 precursor Intestinal trefoil factor hP1 B Homo sapiens Human Trefoil factor 3 precursor Intestinal trefoil factor hP1 B Homo sapiens Human Trefoil factor 3 precursor Intestinal trefoil factor hP1 B Homo sapiens Human Zinc finger protein 295 Zinc finger and BTB domain containing protein 21 Homo sapiens Human Olfactory receptor 10A7 Olfactory receptor OR12 6 Homo sapiens Human Olfactory receptor 10A7 Olfactory receptor OR12 6 Homo sapiens Human Alpha-(1,3)-fucosyltransferase EC 2 4 1 Galactoside 3 L fucosyltransferase Fucosyltransferase 9 FucT IX Homo sapiens Human Complex I intermediate associated protein 30 mitochondrial precursorNADH dehydrogenase ubiquinone 1 alpha subcomplex assembly factor 1 Homo sapiens Human Sorting nexin 22 Homo sapiens Human Olfactory receptor 10A7 Olfactory receptor OR12 6 Homo sapiens Human Hemoglobin subunit gamma 1 Hemoglobin gamma 1 chain Gamma 1 globin Hemoglobin gamma A chain Hb F Agamma Homo sapiens Human Toll-interleukin 1 receptor domain containing adapter protein TIR domain containing adapter protein MyD88 adapter like protein Adaptor protein Wyatt Homo sapiens Human Toll-interleukin 1 receptor domain containing adapter protein TIR domain containing adapter protein MyD88 adapter like protein Adaptor protein Wyatt Homo sapiens Human 116 617 843 443 239 239 239 492 140 140 198 321 169 162 196 515 515 227 1 2 3 4 530 531 1.24 1.23 872 314 532 1.21 533 1.20 534 535 1.18 1.17 536 1.15 537 538 1.12 0.97 539 540 0.95 0.94 541 542 0.93 0.89 543 0.89 544 545 0.87 0.85 546 0.85 547 0.84 Ubiquitin Homo sapiens Human Steroidogenic acute regulatory protein mitochondrial precursor StAR StARD1 Homo sapiens Human Zinc finger protein ZIC 1 Zinc finger protein of the cerebellum 1 Homo sapiens Human Regenerating islet derived protein 4 precursor Reg IV REG like protein Gastrointestinal secretory protein Homo sapiens Human Uncharacterized protein C8orf46 Homo sapiens Human Arginine-glutamic acid dipeptide repeats protein Atrophin 1 like protein Atrophin 1 related protein Homo sapiens Human Keratin, type I cytoskeletal 9 Cytokeratin 9 CK 9 Keratin 9 K9 Homo sapiens Human Protein mago nashi homolog Homo sapiens Human Late cornified envelope protein 3C Late envelope protein 15 Small proline rich like epidermal differentiation complex protein 3A Homo sapiens Human UPF0193 protein EVG1 Homo sapiens Human ER degradation enhancing alpha mannosidase like 1 Homo sapiens Human Frizzled-2 precursor Fz 2 hFz2 FzE2 Homo sapiens Human Putative potassium channel regulatory protein Potassium channel regulator Protein CLLD4 Homo sapiens Human Putative potassium channel regulatory protein Potassium channel regulator Protein CLLD4 Homo sapiens Human Thrombospondin-3 precursor Homo sapiens Human Melanotransferrin precursor Melanoma associated antigen p97 CD228 antigen Homo sapiens Human Melanotransferrin precursor Melanoma associated antigen p97 CD228 antigen Homo sapiens Human Cathepsin E precursor EC 3 4 23 34 Homo sapiens Human 194 548 0.77 Uncharacterized protein C21orf59 Homo sapiens Human 429 549 0.73 389 550 551 0.70 0.66 552 0.65 553 0.65 554 555 0.63 0.57 Inositol polyphosphate multikinase EC 2 7 1 151 Inositol 1 3 4 6 tetrakisphosphate 5 kinase Homo sapiens Human Protein FAM101B Homo sapiens Human Williams-Beuren syndrome chromosome region 23 protein Homo sapiens Human Orphan nuclear receptor EAR 2 V erbA related protein EAR 2 Homo sapiens Human Orphan nuclear receptor EAR 2 V erbA related protein EAR 2 Homo sapiens Human Sodium-dependent E3 ubiquitin protein ligase RING1 EC 6 3 2 Polycomb complex protein RING1 RING finger protein 1 Homo sapiens Human 234 416 257 334 412 405 227 216 578 607 183 183 126 232 232 291 302 149 149 179 450 228 1 2 3 4 556 0.55 217 557 0.55 558 0.51 559 560 0.48 0.45 561 0.42 562 0.36 cAMP-dependent protein kinase inhibitor alpha PKI alpha cAMP dependent protein kinase inhibitor muscle brain isoform Homo sapiens Human cAMP-dependent protein kinase inhibitor alpha PKI alpha cAMP dependent protein kinase inhibitor muscle brain isoform Homo sapiens Human G-protein-signaling modulator 1 Activator of G protein signaling 3 Homo sapiens Human Homeobox protein GSH 1 Homo sapiens Human Acyl-coenzyme A thioesterase 12 EC 3 1 2 1 Acyl CoA thioesterase 12 Acyl CoA thioester hydrolase 12 Cytoplasmic acetyl CoA hydrolase 1 CACH 1 hCACH 1 START domain containing protein 12 StARD12 Homo sapiens Human Small nuclear ribonucleoprotein Sm D2 snRNP core protein D2 Sm D2 Homo sapiens Human Embryonic growth differentiation factor 1 precursor GDF 1 Homo sapiens Human 217 625 871 225 506 681 229 Ɍɚɛɥɢɰɚ 6 ȼɟɪɨɹɬɧɨɫɬɶ ʋ ɩ/ɩ ɫɨɜɩɚɞɟɧɢɹ (%) 1 2 1 90.17 2 87.80 3 45.58 4 44.70 5 43.18 6 42.89 7 8 42.31 41.41 9 39.39 10 11 38.24 35.17 12 34.91 13 31.55 14 30.40 15 29.82 16 17 29.21 26.86 18 26.73 19 26.53 20 25.88 ID ɛɟɥɤɨɜ ɞɥɹ CD34+ȽɋɄ (3-ɹ ɮɪɚɤɰɢɹ, 2-ɹ ɩɨɜɬɨɪɧɨɫɬɶ) ɇɨɦɟɪ ɩɹɬɧɚ 3 4 Immunoglobulin superfamily member 8 precursor CD81 partner 3 Glu Trp Ile EWI motif containing protein 2 EWI 2 Keratinocytes associated transmembrane protein 4 KCT 4 LIR D1 CD316 antigen Homo sapiens Human Selenocysteine-specific elongation factor Elongation factor sec Eukaryotic elongation factor selenocysteine tRNA specific Homo sapiens Human Actin-binding Rho activating protein Striated muscle activator of Rho dependent signaling STARS Homo sapiens Human Nuclear pore complex protein Nup153 Nucleoporin Nup153 153 kDa nucleoporin Homo sapiens Human Actin-binding Rho activating protein Striated muscle activator of Rho dependent signaling STARS Homo sapiens Human Actin-binding Rho activating protein Striated muscle activator of Rho dependent signaling STARS Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human Actin-binding Rho activating protein Striated muscle activator of Rho dependent signaling STARS Homo sapiens Human Actin-binding Rho activating protein Striated muscle activator of Rho dependent signaling STARS Homo sapiens Human Lamin-B2 Homo sapiens Human Actin-binding Rho activating protein Striated muscle activator of Rho dependent signaling STARS Homo sapiens Human Nuclear pore complex protein Nup153 Nucleoporin Nup153 153 kDa nucleoporin Homo sapiens Human Nuclear pore complex protein Nup153 Nucleoporin Nup153 153 kDa nucleoporin Homo sapiens Human Killer cell immunoglobulin like receptor 2DL2 precursor MHC class I NK cell receptor Natural killer associated transcript 6 NKAT 6 p58 natural killer cell receptor clone CL 43 p58 NK receptor Homo sapiens Human Actin-binding Rho activating protein Striated muscle activator of Rho dependent signaling STARS Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human Nuclear pore complex protein Nup153 Nucleoporin Nup153 153 kDa nucleoporin Homo sapiens Human Actin-binding Rho activating protein Striated muscle activator of Rho dependent signaling STARS Homo sapiens Human Bcl-2-modifying factor Homo sapiens Human 12902 Nuclear pore complex protein Nup153 Nucleoporin Nup153 153 kDa nucleoporin Homo sapiens Human 12805 13205 12815 13101 13197 12990 12914 12811 12901 12933 12889 12946 12924 12923 13014 12844 13066 12831 12836 230 1 2 3 4 21 25.65 13060 22 23.22 23 23.03 24 25 22.71 22.61 26 22.38 27 22.21 28 21.73 29 21.60 30 21.36 31 20.81 32 20.60 33 20.56 34 20.53 35 20.31 36 20.16 37 20.07 38 19.55 39 19.40 40 19.36 41 18.21 42 18.18 43 18.00 Nuclear pore complex protein Nup153 Nucleoporin Nup153 153 kDa nucleoporin Homo sapiens Human Glycerol-3-phosphate acyltransferase mitochondrial precursor EC 2 3 1 15 GPAT Homo sapiens Human Actin-binding Rho activating protein Striated muscle activator of Rho dependent signaling STARS Homo sapiens Human Band 4 1 like protein 4A Protein NBL4 Homo sapiens Human Nuclear pore complex protein Nup153 Nucleoporin Nup153 153 kDa nucleoporin Homo sapiens Human E3 ubiquitin protein ligase RNF19 EC 6 3 2 RING finger protein 19 Dorfin Double ring finger protein p38 protein Homo sapiens Human Actin-binding Rho activating protein Striated muscle activator of Rho dependent signaling STARS Homo sapiens Human Cadherin-like protein 26 precursor Cadherin like protein VR20 Homo sapiens Human Actin-binding Rho activating protein Striated muscle activator of Rho dependent signaling STARS Homo sapiens Human Zinc finger BED domain containing protein 4 Homo sapiens Human Rho guanine nucleotide exchange factor 5 Guanine nucleotide regulatory protein TIM Oncogene TIM p60 TIM Transforming immortalized mammary oncogene Homo sapiens Human Actin-binding Rho activating protein Striated muscle activator of Rho dependent signaling STARS Homo sapiens Human Nuclear pore complex protein Nup153 Nucleoporin Nup153 153 kDa nucleoporin Homo sapiens Human Nuclear pore complex protein Nup153 Nucleoporin Nup153 153 kDa nucleoporin Homo sapiens Human Zinc finger BED domain containing protein 4 Homo sapiens Human Nuclear pore complex protein Nup153 Nucleoporin Nup153 153 kDa nucleoporin Homo sapiens Human Actin-binding Rho activating protein Striated muscle activator of Rho dependent signaling STARS Homo sapiens Human Actin-binding Rho activating protein Striated muscle activator of Rho dependent signaling STARS Homo sapiens Human Neuromedin-U receptor 1 NMU R1 G protein coupled receptor 66 G protein coupled receptor FM 3 Homo sapiens Human Nuclear pore complex protein Nup153 Nucleoporin Nup153 153 kDa nucleoporin Homo sapiens Human Actin-binding Rho activating protein Striated muscle activator of Rho dependent signaling STARS Homo sapiens Human Nuclear pore complex protein Nup153 Nucleoporin Nup153 153 kDa nucleoporin Homo sapiens Human Bcl-2-modifying factor Homo sapiens Human 12860 12912 13057 12911 12814 13166 12798 13167 12855 13056 12791 12870 12909 12837 12858 13200 13078 12884 12908 12929 12925 12896 231 1 2 3 4 44 16.83 13196 45 16.29 46 47 15.87 15.81 48 49 50 15.79 14.93 14.83 51 14.60 52 53 14.55 14.17 54 13.86 55 13.72 56 13.65 57 13.18 58 12.78 59 12.51 60 12.41 61 12.35 62 12.21 63 64 12.04 11.60 65 11.19 66 67 10.95 10.85 68 10.59 69 10.58 Uncharacterized protein C18orf54 precursor Homo sapiens Human PH domain leucine rich repeat protein phosphatase like EC 3 1 3 16 Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human Actin-binding Rho activating protein Striated muscle activator of Rho dependent signaling STARS Homo sapiens Human Bcl-2-modifying factor Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human Nuclear pore complex protein Nup153 Nucleoporin Nup153 153 kDa nucleoporin Homo sapiens Human Myosin-Ia Brush border myosin I BBM I BBMI Myosin I heavy chain MIHC Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human Nuclear pore complex protein Nup153 Nucleoporin Nup153 153 kDa nucleoporin Homo sapiens Human Nuclear pore complex protein Nup153 Nucleoporin Nup153 153 kDa nucleoporin Homo sapiens Human Actin-binding Rho activating protein Striated muscle activator of Rho dependent signaling STARS Homo sapiens Human Actin-binding Rho activating protein Striated muscle activator of Rho dependent signaling STARS Homo sapiens Human Nuclear pore complex protein Nup153 Nucleoporin Nup153 153 kDa nucleoporin Homo sapiens Human Nuclear pore glycoprotein p62 62 kDa nucleoporin Homo sapiens Human Inositol polyphosphate multikinase EC 2 7 1 151 Inositol 1 3 4 6 tetrakisphosphate 5 kinase Homo sapiens Human Nuclear pore complex protein Nup153 Nucleoporin Nup153 153 kDa nucleoporin Homo sapiens Human Actin-binding Rho activating protein Striated muscle activator of Rho dependent signaling STARS Homo sapiens Human Actin-binding Rho activating protein Striated muscle activator of Rho dependent signaling STARS Homo sapiens Human Bcl-2-modifying factor Homo sapiens Human Actin-binding Rho activating protein Striated muscle activator of Rho dependent signaling STARS Homo sapiens Human G-protein-signaling modulator 1 Activator of G protein signaling 3 Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human Putative tyrosine protein phosphatase TPTE EC 3 1 3 48 Transmembrane phosphatase with tensin homology Protein BJ HCC 5 Homo sapiens Human Protein transport protein Sec24D SEC24 related protein D Homo sapiens Human Bcl-2-modifying factor Homo sapiens Human 12872 12957 12907 13106 12978 12838 12894 12988 13117 12968 12900 13173 13054 12921 13131 12890 13116 12932 13041 13063 12879 12951 12934 13027 12945 232 1 2 3 4 70 10.52 13065 71 72 10.48 10.39 73 10.38 74 10.07 75 9.97 76 9.83 77 9.55 78 79 80 9.43 9.38 9.15 81 9.07 82 9.03 83 84 8.69 8.60 85 86 8.46 8.37 87 88 8.34 8.31 89 8.30 90 8.15 91 8.01 92 8.01 Nuclear pore complex protein Nup153 Nucleoporin Nup153 153 kDa nucleoporin Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human Ladinin 1 Lad 1 120 kDa linear IgA bullous dermatosis antigen 97 kDa linear IgA bullous dermatosis antigen Linear IgA disease antigen homolog LadA Homo sapiens Human Solute carrier family 2 facilitated glucose transporter member 10 Glucose transporter type 10 Homo sapiens Human Olfactory receptor 10A7 Olfactory receptor OR12 6 Homo sapiens Human Uncharacterized protein C18orf54 precursor Homo sapiens Human Nuclear pore complex protein Nup153 Nucleoporin Nup153 153 kDa nucleoporin Homo sapiens Human Actin-binding Rho activating protein Striated muscle activator of Rho dependent signaling STARS Homo sapiens Human Bcl-2-modifying factor Homo sapiens Human Bcl-2-modifying factor Homo sapiens Human Nuclear pore complex protein Nup153 Nucleoporin Nup153 153 kDa nucleoporin Homo sapiens Human Putative tyrosine protein phosphatase TPTE EC 3 1 3 48 Transmembrane phosphatase with tensin homology Protein BJ HCC 5 Homo sapiens Human Regenerating islet derived protein 4 precursor Reg IV REG like protein Gastrointestinal secretory protein Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human Zinc finger and BTB domain containing protein 41 Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human Anaphase-promoting complex subunit 4 APC4 Cyclosome subunit 4 Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human Probable phospholipid transporting ATPase IF EC 3 6 3 1 ATPase class I type 11B ATPase IR Homo sapiens Human Regenerating islet derived protein 4 precursor Reg IV REG like protein Gastrointestinal secretory protein Homo sapiens Human Nuclear pore complex protein Nup153 Nucleoporin Nup153 153 kDa nucleoporin Homo sapiens Human Putative tyrosine protein phosphatase TPTE EC 3 1 3 48 Transmembrane phosphatase with tensin homology Protein BJ HCC 5 Homo sapiens Human Putative tyrosine protein phosphatase TPTE EC 3 1 3 48 Transmembrane phosphatase with tensin homology Protein BJ HCC 5 Homo sapiens Human 12998 12835 13127 12972 13030 12887 13204 13073 13070 12859 13047 13023 12970 12996 12981 13034 12984 13142 12953 12874 12808 12808 233 1 2 3 4 93 7.92 13141 94 7.87 95 7.78 96 7.58 97 98 7.53 7.46 99 7.31 100 7.29 101 102 7.27 7.17 103 7.02 104 7.00 105 6.95 Selenocysteine-specific elongation factor Elongation factor sec Eukaryotic elongation factor selenocysteine tRNA specific Homo sapiens Human Nuclear pore complex protein Nup153 Nucleoporin Nup153 153 kDa nucleoporin Homo sapiens Human Arginine-glutamic acid dipeptide repeats protein Atrophin 1 like protein Atrophin 1 related protein Homo sapiens Human Chondroitin sulfate glucuronyltransferase EC 2 4 1 226 N acetylgalactosaminyl proteoglycan 3 beta glucuronosyltransferase Chondroitin glucuronyltransferase II CSGlcA T Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human Protein BEX1 Brain expressed X linked protein 1 Homo sapiens Human Putative tyrosine protein phosphatase TPTE EC 3 1 3 48 Transmembrane phosphatase with tensin homology Protein BJ HCC 5 Homo sapiens Human Nuclear pore complex protein Nup153 Nucleoporin Nup153 153 kDa nucleoporin Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human Actin-binding Rho activating protein Striated muscle activator of Rho dependent signaling STARS Homo sapiens Human G-protein-signaling modulator 1 Activator of G protein signaling 3 Homo sapiens Human Rho guanine nucleotide exchange factor 5 Guanine nucleotide regulatory protein TIM Oncogene TIM p60 TIM Transforming immortalized mammary oncogene Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human 106 6.89 Keratin-associated protein 21 2 Homo sapiens Human 107 6.88 108 6.86 HMG box containing protein 1 HMG box transcription factor 13121 1 High mobility group box transcription factor 1 Homo sapiens Human Nuclear pore complex protein Nup153 Nucleoporin Nup153 12904 153 kDa nucleoporin Homo sapiens Human 109 6.85 110 6.67 111 6.67 112 6.66 13090 12862 13084 12987 13076 13111 13048 12969 13119 12821 13124 12982 12960 Actin-binding Rho activating protein Striated muscle activator 13104 of Rho dependent signaling STARS Homo sapiens Human Selenocysteine-specific elongation factor Elongation factor sec 12916 Eukaryotic elongation factor selenocysteine tRNA specific Homo sapiens Human Selenocysteine-specific elongation factor Elongation factor sec 12916 Eukaryotic elongation factor selenocysteine tRNA specific Homo sapiens Human Sterol regulatory element binding protein 1 SREBP 1 Sterol 13197 regulatory element binding transcription factor 1 Homo sapiens Human 234 1 2 3 4 113 6.65 12952 114 6.65 115 116 117 118 119 120 121 6.54 6.51 6.49 6.48 6.48 6.46 6.37 122 6.33 123 6.32 124 6.21 125 6.21 126 6.16 127 6.13 128 6.11 129 6.10 130 6.05 131 6.04 132 6.01 Nuclear pore complex protein Nup153 Nucleoporin Nup153 153 kDa nucleoporin Homo sapiens Human Nuclear pore complex protein Nup153 Nucleoporin Nup153 153 kDa nucleoporin Homo sapiens Human Bcl-2-modifying factor Homo sapiens Human L-myc-1 proto oncogene protein Homo sapiens Human Uncharacterized protein C2orf21 Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human Band 4 1 like protein 4A Protein NBL4 Homo sapiens Human Actin-binding Rho activating protein Striated muscle activator of Rho dependent signaling STARS Homo sapiens Human Cadherin-like protein 26 precursor Cadherin like protein VR20 Homo sapiens Human Protein BEX1 Brain expressed X linked protein 1 Homo sapiens Human Pantothenate kinase 3 EC 2 7 1 33 Pantothenic acid kinase 3 hPanK3 Homo sapiens Human Pantothenate kinase 3 EC 2 7 1 33 Pantothenic acid kinase 3 hPanK3 Homo sapiens Human Actin-binding Rho activating protein Striated muscle activator of Rho dependent signaling STARS Homo sapiens Human Glial fibrillary acidic protein astrocyte GFAP Homo sapiens Human Oligodendrocyte transcription factor 1 Oligo1 Homo sapiens Human Inositol polyphosphate multikinase EC 2 7 1 151 Inositol 1 3 4 6 tetrakisphosphate 5 kinase Homo sapiens Human G-protein-signaling modulator 1 Activator of G protein signaling 3 Homo sapiens Human Ladinin 1 Lad 1 120 kDa linear IgA bullous dermatosis antigen 97 kDa linear IgA bullous dermatosis antigen Linear IgA disease antigen homolog LadA Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human 133 5.92 Transmembrane protein 106B Homo sapiens Human 12962 134 5.91 13172 135 5.84 136 5.83 137 5.76 Immunoglobulin superfamily member 8 precursor CD81 partner 3 Glu Trp Ile EWI motif containing protein 2 EWI 2 Keratinocytes associated transmembrane protein 4 KCT 4 LIR D1 CD316 antigen Homo sapiens Human Putative tyrosine protein phosphatase TPTE EC 3 1 3 48 Transmembrane phosphatase with tensin homology Protein BJ HCC 5 Homo sapiens Human Prostaglandin D2 receptor Prostanoid DP receptor PGD receptor Homo sapiens Human Uncharacterized protein C2orf21 Homo sapiens Human 12952 13087 13151 12839 12989 12989 13039 13082 12883 13162 12986 12986 13170 12829 12863 12944 12849 12828 12955 13208 12977 12927 235 1 2 3 4 138 5.74 13126 139 140 5.66 5.58 141 142 5.52 5.46 143 144 145 5.43 5.40 5.38 146 5.32 147 5.31 Nuclear pore complex protein Nup153 Nucleoporin Nup153 153 kDa nucleoporin Homo sapiens Human 40S ribosomal protein S12 Homo sapiens Human Regenerating islet derived protein 4 precursor Reg IV REG like protein Gastrointestinal secretory protein Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human Actin-binding Rho activating protein Striated muscle activator of Rho dependent signaling STARS Homo sapiens Human Uncharacterized protein C2orf21 Homo sapiens Human Band 4 1 like protein 4A Protein NBL4 Homo sapiens Human Immunoglobulin superfamily member 8 precursor CD81 partner 3 Glu Trp Ile EWI motif containing protein 2 EWI 2 Keratinocytes associated transmembrane protein 4 KCT 4 LIR D1 CD316 antigen Homo sapiens Human Arginine-glutamic acid dipeptide repeats protein Atrophin 1 like protein Atrophin 1 related protein Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human 148 5.31 Keratin-associated protein 21 2 Homo sapiens Human 13013 149 5.28 13136 150 151 5.26 5.24 152 5.23 153 4.93 Nuclear pore complex protein Nup153 Nucleoporin Nup153 153 kDa nucleoporin Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human Nuclear pore complex protein Nup153 Nucleoporin Nup153 153 kDa nucleoporin Homo sapiens Human Transcription factor AP 2 alpha AP2 alpha Activating enhancer binding protein 2 alpha AP 2 transcription factor Activator protein 2 AP 2 Homo sapiens Human Collagen alpha 1 XVI chain precursor Homo sapiens Human 13025 154 4.93 Collagen alpha 1 XVI chain precursor Homo sapiens Human 13025 155 4.89 12920 156 157 4.88 4.83 158 4.81 159 4.70 160 161 4.65 4.59 162 4.58 163 4.46 Phosphofurin acidic cluster sorting protein 2 PACS 2 PACS1 like protein Homo sapiens Human Transmembrane protein 106BHomo sapiens Human Ladinin 1 Lad 1 120 kDa linear IgA bullous dermatosis antigen 97 kDa linear IgA bullous dermatosis antigen Linear IgA disease antigen homolog LadA Homo sapiens Human Methionyl-tRNA synthetase cytoplasmic EC 6 1 1 10 Methionine tRNA ligase MetRS Homo sapiens Human Gamma crystallin C Gamma crystallin 2 1 Gamma crystallin 3 Homo sapiens Human Frizzled-7 precursor Fz 7 hFz7 FzE3 Homo sapiens Human Inositol polyphosphate multikinase EC 2 7 1 151 Inositol 1 3 4 6 tetrakisphosphate 5 kinase Homo sapiens Human Low-density lipoprotein receptor related protein 8 precursor Apolipoprotein E receptor 2 Homo sapiens Human Bcl-2-modifying factor Homo sapiens Human 13175 12958 12975 12868 12818 12880 13046 13043 13013 12995 12922 13209 12959 12938 13091 12878 12948 12903 13105 13040 236 1 2 3 4 164 4.44 13138 165 4.41 166 4.41 167 4.40 168 4.33 169 170 171 4.30 4.22 4.20 172 4.18 173 4.17 174 4.16 175 4.16 176 4.11 177 4.07 178 179 180 181 4.04 4.04 4.02 3.98 182 3.98 183 184 185 3.92 3.88 3.78 186 3.78 PCI domain containing protein 2 CSN12 like protein Homo sapiens Human Transcription factor AP 2 alpha AP2 alpha Activating enhancer binding protein 2 alpha AP 2 transcription factor Activator protein 2 AP 2 Homo sapiens Human Transcription factor AP 2 alpha AP2 alpha Activating enhancer binding protein 2 alpha AP 2 transcription factor Activator protein 2 AP 2 Homo sapiens Human Complex I intermediate associated protein 30 mitochondrial precursor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly factor 1 Homo sapiens Human Retinol dehydrogenase 12 EC 1 1 1 All trans and 9 cis retinol dehydrogenase Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human Uncharacterized protein C2orf14 Homo sapiens Human Olfactory receptor 10A7 Olfactory receptor OR12 6 Homo sapiens Human Probable G protein coupled receptor 61 Biogenic amine receptor like G protein coupled receptor Homo sapiens Human Putative ATP dependent RNA helicase DHX33 EC 3 6 1 DEAH box protein 33 Homo sapiens Human Complex I intermediate associated protein 30 mitochondrial precursor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly factor 1 Homo sapiens Human Complex I intermediate associated protein 30 mitochondrial precursor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly factor 1 Homo sapiens Human Olfactory receptor 10A7 Olfactory receptor OR12 6 Homo sapiens Human Thromboxane A2 receptor TXA2 R Prostanoid TP receptor Homo sapiens Human Uncharacterized protein C2orf21 Homo sapiens Human Uncharacterized protein C2orf21 Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human Ladinin 1 Lad 1 120 kDa linear IgA bullous dermatosis antigen 97 kDa linear IgA bullous dermatosis antigen Linear IgA disease antigen homolog LadA Homo sapiens Human Ladinin 1 Lad 1 120 kDa linear IgA bullous dermatosis antigen 97 kDa linear IgA bullous dermatosis antigen Linear IgA disease antigen homolog LadA Homo sapiens Human Transmembrane protein 106B Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human Uncharacterized protein C18orf54 precursor Homo sapiens Human Uncharacterized protein C18orf54 precursor Homo sapiens Human 12926 12926 13067 13109 13004 13154 13016 13168 12891 12832 12832 12939 13201 13031 13031 12999 12966 12966 13026 13005 12803 12803 237 1 2 3 4 187 3.76 12840 188 3.71 189 3.65 190 3.63 191 3.56 192 3.53 193 3.51 194 195 196 197 198 3.47 3.42 3.33 3.31 3.28 199 3.28 200 3.25 201 3.23 202 3.22 203 3.18 204 3.17 205 206 3.16 3.15 207 3.12 Regenerating islet derived protein 4 precursor Reg IV REG like protein Gastrointestinal secretory protein Homo sapiens Human B lymphocyte activation related protein BC 1514 Homo sapiens Human Cytochrome P450 4F8 EC 1 14 14 1 CYPIVF8 Homo sapiens Human Reticulon-2 Neuroendocrine specific protein like 1 NSP like protein 1 NSPLI Homo sapiens Human Chondroitin sulfate glucuronyltransferase EC 2 4 1 226 N acetylgalactosaminyl proteoglycan 3 beta glucuronosyltransferase Chondroitin glucuronyltransferase II CSGlcA T Homo sapiens Human Regenerating islet derived protein 4 precursor Reg IV REG like protein Gastrointestinal secretory protein Homo sapiens Human Nuclear pore complex protein Nup153 Nucleoporin Nup153 153 kDa nucleoporin Homo sapiens Human 40S ribosomal protein S12 Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human Protein yippee like 4 Homo sapiens Human ER degradation enhancing alpha mannosidase like 1 Homo sapiens Human ER degradation enhancing alpha mannosidase like 1 Homo sapiens Human Zinc finger BED domain containing protein 4 Homo sapiens Human Killer cell immunoglobulin like receptor 2DL2 precursor MHC class I NK cell receptor Natural killer associated transcript 6 NKAT 6 p58 natural killer cell receptor clone CL 43 p58 NK receptor Homo sapiens Human Regenerating islet derived protein 4 precursor Reg IV REG like protein Gastrointestinal secretory protein Homo sapiens Human Prolactin regulatory element binding protein Mammalian guanine nucleotide exchange factor mSec12 Homo sapiens Human Reticulon-2 Neuroendocrine specific protein like 1 NSP like protein 1 NSPLI Homo sapiens Human Ras-related protein Ral B Homo sapiens Human Putative ATP dependent RNA helicase DHX33 EC 3 6 1 DEAH box protein 33 Homo sapiens Human Frizzled-2 precursor Fz 2 hFz2 FzE2 Homo sapiens Human 208 3.08 L-myc-1 proto oncogene protein Homo sapiens Human 13129 13149 12871 12898 12842 13038 12906 12983 12976 13033 13050 13050 12848 13088 12865 13140 13095 13152 12905 13035 13122 238 1 2 3 4 209 3.07 13032 210 3.07 211 3.06 212 3.06 213 3.05 214 2.92 215 2.91 216 217 2.85 2.83 218 2.81 219 2.79 220 2.79 221 222 2.76 2.72 223 2.71 224 2.59 225 2.58 226 227 2.57 2.56 228 229 2.50 2.49 230 2.44 Olfactory receptor 10A7 Olfactory receptor OR12 6 Homo sapiens Human Olfactory receptor 10A7 Olfactory receptor OR12 6 Homo sapiens Human Vacuolar protein sorting associated protein 25 hVps25 ELL associated protein of 20 kDa Dermal papilla derived protein 9 Homo sapiens Human Vacuolar protein sorting associated protein 25 hVps25 ELL associated protein of 20 kDa Dermal papilla derived protein 9 Homo sapiens Human Oligodendrocyte transcription factor 1 Oligo1 Homo sapiens Human Actin-binding Rho activating protein Striated muscle activator of Rho dependent signaling STARS Homo sapiens Human Ladinin 1 Lad 1 120 kDa linear IgA bullous dermatosis antigen 97 kDa linear IgA bullous dermatosis antigen Linear IgA disease antigen homolog LadA Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human Cystatin-S precursor Cystatin 4 Salivary acidic protein 1 Cystatin SA III Homo sapiens Human Nuclear pore complex protein Nup153 Nucleoporin Nup153 153 kDa nucleoporin Homo sapiens Human Complex I intermediate associated protein 30 mitochondrial precursor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly factor 1 Homo sapiens Human Complex I intermediate associated protein 30 mitochondrial precursor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly factor 1 Homo sapiens Human Protein mago nashi homolog Homo sapiens Human Oligodendrocyte transcription factor 1 Oligo1 Homo sapiens Human Regenerating islet derived protein 4 precursor Reg IV REG like protein Gastrointestinal secretory protein Homo sapiens Human Trefoil factor 3 precursor Intestinal trefoil factor hP1 B Homo sapiens Human Arachidonate 15 lipoxygenase type II EC 1 13 11 33 15 LOX 2 15 lipoxygenase 2 Homo sapiens Human Testis-expressed sequence 10 protein Homo sapiens Human Nuclear pore complex protein Nup153 Nucleoporin Nup153 153 kDa nucleoporin Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human Presequence protease mitochondrial precursor EC 3 4 24 hPreP Pitrilysin metalloproteinase 1 Metalloprotease 1 hMP1 Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human 13032 12943 12943 13069 13055 13044 12973 12899 13206 12866 12866 13042 12893 13098 12974 13156 13159 13058 12965 12875 12950 239 1 2 3 4 231 2.41 13022 232 2.41 233 234 235 236 2.40 2.40 2.38 2.37 237 2.35 238 239 240 2.33 2.33 2.26 241 2.22 242 2.22 243 2.21 244 245 246 2.18 2.18 2.14 247 2.08 248 2.05 249 2.03 250 2.03 251 252 2.01 1.90 253 1.87 Olfactory receptor 10A7 Olfactory receptor OR12 6 Homo sapiens Human Olfactory receptor 10A7 Olfactory receptor OR12 6 Homo sapiens Human Angiopoietin-1 precursor ANG 1 Homo sapiens Human Angiopoietin-1 precursor ANG 1 Homo sapiens Human Olfactory receptor 52E2 Homo sapiens Human Transcription factor AP 2 alpha AP2 alpha Activating enhancer binding protein 2 alpha AP 2 transcription factor Activator protein 2 AP 2 Homo sapiens Human Killer cell immunoglobulin like receptor 2DL2 precursor MHC class I NK cell receptor Natural killer associated transcript 6 NKAT 6 p58 natural killer cell receptor clone CL 43 p58 NK receptor Homo sapiens Human Nucleolar protein 66 hsNO66 Homo sapiens Human Nucleolar protein 66 hsNO66 Homo sapiens Human Nucleolar protein NOP5 Nucleolar protein 5 NOP58 Homo sapiens Human Regenerating islet derived protein 4 precursor Reg IV REG like protein Gastrointestinal secretory protein Homo sapiens Human Regenerating islet derived protein 4 precursor Reg IV REG like protein Gastrointestinal secretory protein Homo sapiens Human Regenerating islet derived protein 4 precursor Reg IV REG like protein Gastrointestinal secretory protein Homo sapiens Human Protein yippee like 4 Homo sapiens Human Protein yippee like 4 Homo sapiens Human Trefoil factor 3 precursor Intestinal trefoil factor hP1 B Homo sapiens Human Germinal center B cell expressed transcript 2 protein Germinal center associated lymphoma protein hGAL Homo sapiens Human Cadherin-like protein 26 precursor Cadherin like protein VR20 Homo sapiens Human Zinc finger BED domain containing protein 4 Homo sapiens Human Zinc finger BED domain containing protein 4 Homo sapiens Human Secretagogin Homo sapiens Human Killer cell immunoglobulin like receptor 2DL2 precursor MHC class I NK cell receptor Natural killer associated transcript 6 NKAT 6 p58 natural killer cell receptor clone CL 43 p58 NK receptor Homo sapiens Human Uncharacterized protein C1orf50 Homo sapiens Human 13022 12850 12850 12994 13207 13161 13045 13045 13144 13021 13021 13075 12806 12806 13008 13143 12886 12882 12882 12873 13139 13062 240 1 2 3 4 254 1.86 12843 255 1.83 256 1.79 257 1.76 258 1.76 259 1.74 260 1.73 261 1.65 262 1.63 263 1.62 264 1.58 265 1.52 266 1.51 267 268 269 1.50 1.50 1.48 270 1.47 271 1.44 272 1.41 273 1.38 274 275 276 1.32 1.27 1.26 YTH domain containing protein 1 Putative splicing factor YT521 Homo sapiens Human HLA class II histocompatibility antigen DM beta chain precursor MHC class II antigen DMB Homo sapiens Human Selenocysteine-specific elongation factor Elongation factor sec Eukaryotic elongation factor selenocysteine tRNA specific Homo sapiens Human Inositol polyphosphate multikinase EC 2 7 1 151 Inositol 1 3 4 6 tetrakisphosphate 5 kinase Homo sapiens Human Inositol polyphosphate multikinase EC 2 7 1 151 Inositol 1 3 4 6 tetrakisphosphate 5 kinase Homo sapiens Human Complex I intermediate associated protein 30 mitochondrial precursor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly factor 1 Homo sapiens Human Oligodendrocyte transcription factor 1 Oligo1 Homo sapiens Human Arachidonate 15 lipoxygenase type II EC 1 13 11 33 15 LOX 2 15 lipoxygenase 2 Homo sapiens Human Methionyl-tRNA synthetase cytoplasmic EC 6 1 1 10 Methionine tRNA ligase MetRS Homo sapiens Human Cadherin-like protein 26 precursor Cadherin like protein VR20 Homo sapiens Human HLA class II histocompatibility antigen DM beta chain precursor MHC class II antigen DMB Homo sapiens Human Ladinin 1 Lad 1 120 kDa linear IgA bullous dermatosis antigen 97 kDa linear IgA bullous dermatosis antigen Linear IgA disease antigen homolog LadA Homo sapiens Human Serine/threonine-protein kinase Pim 3 EC 2 7 11 1 Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human Keratin-associated protein 21 2 Homo sapiens Human E3 ubiquitin protein ligase RNF19 EC 6 3 2 RING finger protein 19 Dorfin Double ring finger protein p38 protein Homo sapiens Human Transmembrane gamma carboxyglutamic acid protein 1 precursor Proline rich Gla protein 1 Proline rich gamma carboxyglutamic acid protein 1 Homo sapiens Human Arachidonate 15 lipoxygenase type II EC 1 13 11 33 15 LOX 2 15 lipoxygenase 2 Homo sapiens Human Acyl-CoA-binding domain containing protein 7 Homo sapiens Human Elongation factor Tu mitochondrial precursor EF Tu P43 Homo sapiens Human Oncostatin-M precursor OSM Homo sapiens Human Protein yippee like 4 Homo sapiens Human UPF0318 protein FAM120A Homo sapiens Human 13163 12861 13097 13097 13012 12841 12928 13079 13009 13089 12854 13100 12992 12992 12851 13052 12917 13001 13133 13171 13006 12919 241 1 2 3 4 277 1.23 12856 278 1.18 279 1.07 280 1.05 281 0.99 282 0.94 283 284 0.86 0.84 285 0.63 286 0.62 287 0.62 288 0.59 289 0.54 290 0.48 Steroidogenic acute regulatory protein mitochondrial precursor StAR StARD1 Homo sapiens Human Breast carcinoma amplified sequence 1 Novel amplified in breast cancer 1 Amplified and overexpressed in breast cancer Homo sapiens Human Syntaxin-binding protein 1 Unc 18 homolog Unc 18A Unc 18 1 N Sec1 p67 Homo sapiens Human Guanylyl cyclase activating protein 3 GCAP 3 Guanylate cyclase activator 1C Homo sapiens Human Glypican-3 precursor Intestinal protein OCI 5 GTR2 2 MXR7 Homo sapiens Human Zinc finger protein 148 Zinc finger DNA binding protein 89 Transcription factor ZBP 89 Homo sapiens Human Protein Dom3Z Dom 3 homolog Z Homo sapiens Human Desmoglein-3 precursor 130 kDa pemphigus vulgaris antigen PVA Homo sapiens Human Protein transport protein Sec24D SEC24 related protein D Homo sapiens Human Aldehyde dehydrogenase dimeric NADP preferring EC 1 2 1 5 ALDH class 3 ALDHIII Homo sapiens Human Aldehyde dehydrogenase dimeric NADP preferring EC 1 2 1 5 ALDH class 3 ALDHIII Homo sapiens Human Protein arginine N methyltransferase 6 EC 2 1 1 Heterogeneous nuclear ribonucleoprotein methyltransferase like protein 6 Homo sapiens Human Cyclin-dependent kinases regulatory subunit 1 CKS 1 Homo sapiens Human Dickkopf-like protein 1 precursor Soggy 1 protein SGY 1 Homo sapiens Human 13199 13099 12985 13150 13072 12915 12930 13103 13068 13068 12980 13157 12993 242 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