Zuo Yongchun, Su Guanghua, Cheng Lei, Liu Kun, Feng Yu, Wei Zhuying, Bai Chunling, Cao Guifang, Li Guangpeng
The Research Center for Laboratory Animal Science, College of Life Sciences, Inner Mongolia University, Hohhot 010021, China.
College of Veterinary Medicine, Inner Mongolia Agricultural University, Hohhot 010018, China.
Oncotarget. 2017 Jul 22;8(39):65847-65859. doi: 10.18632/oncotarget.19504. eCollection 2017 Sep 12.
The success of cloned animal "Dolly Sheep" demonstrated the somatic cell nuclear transfer (SCNT) technique holds huge potentials for mammalian asexual reproduction. However, the extremely poor development of SCNT embryos indicates their molecular mechanism remain largely unexplored. Deciphering the spatiotemporal patterns of gene expression in SCNT embryos is a crucial step toward understanding the mechanisms associated with nuclear reprogramming. In this study, a valuable transcriptome recourse of SCNT embryos was firstly established, which derived from different inter-/intra donor cells. The gene co-expression analysis identified 26 cell-specific modules, and a series of regulatory pathways related to reprogramming barriers were further enriched. Compared to the intra-SCNT embryos, the inter-SCNT embryos underwent only complete partially reprogramming. As master genome trigger genes, the transcripts related to TFIID subunit, RNA polymerase and mediators were incomplete activated in inter-SCNT embryos. The inter-SCNT embryos only wasted the stored maternal mRNA of master regulators, but failed to activate their self-sustained pathway of RNA polymerases. The KDM family of epigenetic regulator also seriously delayed in inter-SCNT embryo reprogramming process. Our study provided new insight into understanding of the mechanisms of nuclear reprogramming.
克隆动物“多利羊”的成功表明，体细胞克隆技术在哺乳动物无性繁殖方面具有巨大潜力。然而，体细胞克隆胚胎的发育极差，这表明其分子机制在很大程度上仍未被探索。解析体细胞克隆胚胎中基因表达的时空模式是理解与核重编程相关机制的关键一步。在本研究中，首先建立了一个有价值的体细胞克隆胚胎转录组资源库，该资源库来源于不同的供体细胞间/供体细胞内。基因共表达分析确定了26个细胞特异性模块，并进一步富集了一系列与重编程障碍相关的调控途径。与供体细胞内克隆胚胎相比，供体细胞间克隆胚胎仅经历了部分完全重编程。作为主要基因组触发基因，与TFIID亚基、RNA聚合酶和中介体相关的转录本在供体细胞间克隆胚胎中未被完全激活。供体细胞间克隆胚胎仅消耗了主要调控因子储存的母体mRNA，但未能激活其自身维持的RNA聚合酶途径。表观遗传调节因子的KDM家族在供体细胞间克隆胚胎重编程过程中也严重延迟。我们的研究为理解核重编程机制提供了新的见解。
