Terminally differentiated somatic cells can be reprogrammed into a totipotent state through somatic cell nuclear transfer (SCNT). The incomplete reprogramming is the major reason for developmental arrest of SCNT embryos at early stages. In our studies, we found that pathways for autophagy, endocytosis, and apoptosis were incompletely activated in nuclear transfer (NT) 2-cell arrest embryos, whereas extensively inhibited pathways for stem cell pluripotency maintenance, DNA repair, cell cycle, and autophagy may result in NT 4-cell embryos arrest. As for NT normal embryos, a significant shift in expression of developmental transcription factors (TFs) Id1, Pou6f1, Cited1, and Zscan4c was observed. Compared with pluripotent gene Ascl2 being activated only in NT 2-cell, Nanog, Dppa2, and Sall4 had major expression waves in normal development of both NT 2-cell and 4-cell embryos. Additionally, Kdm4b/4d and Kdm5b had been confirmed as key markers in NT 2-cell and 4-cell embryos, respectively. Histone acetylases Kat8, Elp6, and Eid1 were co-activated in NT 2-cell and 4-cell embryos to facilitate normal development. Gadd45a as a key driver functions with Tet1 and Tet2 to improve the efficiency of NT reprogramming. Taken together, our findings provided an important theoretical basis for elucidating the potential molecular mechanisms and identified reprogramming driver factor to improve the efficiency of SCNT reprogramming.

终末分化的体细胞可以通过体细胞核移植（SCNT）重新编程为全能状态。不完全的重编程是在早期阶段SCNT胚胎发育停滞的主要原因。在我们的研究中，我们发现自噬，内吞和凋亡途径在核转移（NT）2细胞阻滞胚胎中未完全激活，而干细胞多能性维持，DNA修复，细胞周期和自噬的广泛抑制途径可能会导致在NT 4细胞胚胎中停滞。至于NT正常胚胎，观察到发育转录因子（TFs）Id1，Pou6f1，Cited1和Zscan4c表达的显着变化。与多能基因比较ASCL2被激活只在NT 2细胞，Nanog的，DPPA2，和Sall4这两个NT 2细胞和4细胞胚胎的正常发育有重要表达波。此外，已确认Kdm4b / 4d和Kdm5b分别是NT 2细胞和4细胞胚胎中的关键标记。组蛋白乙酰化酶Kat8，Elp6和Eid1在NT 2细胞和4细胞胚胎中被共同激活，以促进正常发育。Gadd45a作为Tet1和Tet2的主要驱动程序以提高NT重新编程的效率。综上所述，我们的发现为阐明潜在的分子机制提供了重要的理论基础，并确定了重编程驱动因子以提高SCNT的重编程效率。