中南大学林戈课题组、中国医学科学院蒋太交课题组与深圳华大生命科学研究院徐凤萍课题组，共同合作利用对单亲胚胎单细胞转录组分析揭示了母体对人类胚胎着床前发育的影响。相关论文发表于2019年10月3日在线发表于《细胞—干细胞》杂志。

为了研究亲本基因组对早期胚胎发生的贡献，研究人员系统地从1细胞到桑椹胚阶段分析了人类双亲和单亲胚胎的单细胞转录组。研究人员观察到单亲胚胎表现出可变和减少的胚胎基因组激活（EGA）。比较转录组分析在着床前阶段鉴定出807个母本偏向表达基因（MBG）和581个父本偏向表达基因（PBG）。MBG在4细胞阶段变得明显，并有助于EGA的启动，而PBG在8细胞阶段优先出现，并可能影响胚胎的致密性和滋养外胚层分化。调控网络分析显示，DUX4、EGR2和DUXA是MBG表达中的关键转录因子。ZNF263和KLF3对于PBG的表达很重要。

研究人员证明了特定于父母的DNA甲基化可能解释了大多数PBG的表达。这些结果为了解父母的基因组激活提供了宝贵的资源，并可能有助于阐明人类早期发育中的亲源效应。

附：英文原文

Title: Single-Cell Transcriptome Analysis of Uniparental Embryos Reveals Parent-of-Origin Effects on Human Preimplantation Development

Author: Lizhi Leng, Jiya Sun, Jinrong Huang, Fei Gong, Ling Yang, Shuoping Zhang, Xuye Yuan, Fang Fang, Xun Xu, Yonglun Luo, Lars Bolund, Brock A. Peters, Guangxiu Lu, Taijiao Jiang, Fengping Xu, Ge Lin

Issue&Volume: 3 October 2019

Abstract: To investigate the contribution of parental genomes to early embryogenesis, we profiled the single-cell transcriptomes of human biparental and uniparental embryos systematically from the 1-cell to the morula stage. We observed that uniparental embryos exhibited variable and decreased embryonic genome activation (EGA). Comparative transcriptome analysis identified 807 maternally biased expressed genes (MBGs) and 581 paternally biased expressed genes (PBGs) in the preimplantation stages. MBGs became apparent at the 4-cell stage and contributed to the initiation of EGA, whereas PBGs preferentially appeared at the 8-cell stage and might affect embryo compaction and trophectoderm specification. Regulatory network analysis revealed that DUX4, EGR2, and DUXA are key transcription factors in MBGs expression; ZNF263 and KLF3 are important for PBGs expression. We demonstrated that parent-specific DNA methylation might account for the expression of most PBGs. Our results provide a valuable resource to understand parental genome activation and might help to elucidate parent-of-origin effects in early human development.

DOI: 10.1016/j.stem.2019.09.004

Source: https://www.cell.com/cell-stem-cell/fulltext/S1934-5909(19)30389-3