Zhang Chenxi, Li Conghui, Yang Ling, Leng Lizhi, Jovic Dragomirka, Wang Jun, Fang Fang, Li Guibo, Zhao Depeng, Li Xuemei, Lin Lin, Luo Yonglun, Bolund Lars, Huang Jinrong, Lin Ge, Xu Fengping
College of Life Sciences, University of Chinese Academy of Sciences, Beijing, China.
BGI-Shenzhen, Shenzhen, China.
Front Cell Dev Biol. 2021 Sep 17;9:709498. doi: 10.3389/fcell.2021.709498. eCollection 2021.
Previous studies have revealed that transcription factors (TFs) play important roles in biparental (BI) early human embryogenesis. However, the contribution of TFs during early uniparental embryo development is still largely unknown. Here we systematically studied the expression profiles of transcription factors in early embryonic development and revealed the dynamic changes of TFs in human biparental and uniparental embryogenesis by single-cell RNA sequencing (scRNA-seq). In general, the TF expression model of uniparental embryos showed a high degree of conformity with biparental embryos. The detailed network analysis of three different types of embryos identified that 10 out of 17 hub TFs were shared or specifically owned, such as ZNF480, ZNF581, PHB, and POU5F1, were four shared TFs, ZFN534, GTF3A, ZNF771, TEAD4, and LIN28A, were androgenic (AG) specific TFs, and ZFP42 was the only one parthenogenetic (PG) specific TF. All the four shared TFs were validated using human embryonic stem cell (hESC) differentiation experiments; most of their target genes are responsible for stem cell maintenance and differentiation. We also found that Zf-C2H2, HMG, and MYB were three dominant transcription factor families that appeared in early embryogenesis. Altogether, our work provides a comprehensive regulatory framework and better understanding of TF function in human biparental and uniparental embryogenesis.
先前的研究表明,转录因子(TFs)在人类双亲早期胚胎发育中发挥着重要作用。然而,转录因子在单亲胚胎早期发育过程中的作用仍很大程度上未知。在此,我们系统地研究了转录因子在早期胚胎发育中的表达谱,并通过单细胞RNA测序(scRNA-seq)揭示了人类双亲及单亲胚胎发育中转录因子的动态变化。总体而言,单亲胚胎的转录因子表达模式与双亲胚胎高度一致。对三种不同类型胚胎的详细网络分析确定,17个核心转录因子中有10个是共享的或特定的,例如ZNF480、ZNF581、PHB和POU5F1是四个共享转录因子,ZFN534、GTF3A、ZNF771、TEAD4和LIN28A是雄激素性(AG)特异性转录因子,而ZFP42是唯一的孤雌生殖(PG)特异性转录因子。所有这四个共享转录因子均通过人类胚胎干细胞(hESC)分化实验进行了验证;它们的大多数靶基因负责干细胞的维持和分化。我们还发现Zf-C2H2、HMG和MYB是在早期胚胎发育中出现的三个主要转录因子家族。总之,我们的工作提供了一个全面的调控框架,并更好地理解了转录因子在人类双亲及单亲胚胎发育中的功能。