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Single-Cell Transcriptome Analysis of Uniparental Embryos Reveals Parent-of-Origin Effects on Human Preimplantation Development.
Cell Stem Cell ( IF 23.9 ) Pub Date : 2019-10-03 , DOI: 10.1016/j.stem.2019.09.004
Lizhi Leng 1 , Jiya Sun 2 , Jinrong Huang 3 , Fei Gong 1 , Ling Yang 4 , Shuoping Zhang 5 , Xuye Yuan 2 , Fang Fang 6 , Xun Xu 6 , Yonglun Luo 7 , Lars Bolund 7 , Brock A Peters 8 , Guangxiu Lu 9 , Taijiao Jiang 2 , Fengping Xu 3 , Ge Lin 9
Affiliation  

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.



中文翻译:

单细胞转录组分析的单亲胚胎揭示了父本对人类植入前发育的影响。

为了研究亲本基因组对早期胚胎发生的贡献,我们系统地从1细胞到桑ula期对人双亲和单亲胚胎的单细胞转录组进行了分析。我们观察到单亲胚胎表现出可变和减少的胚胎基因组激活(EGA)。比较转录组分析鉴定了在植入前阶段的807个母体偏向表达基因(MBG)和581个母体偏向表达基因(PBG)。MBGs在4细胞阶段变得明显,并有助于EGA的启动,而PBGs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规格。监管网络分析显示,DUX4,EGR2和DUXA是MBG表达中的关键转录因子。ZNF263和KLF3对PBG的表达很重要。我们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。我们的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起源父母效应。

更新日期:2019-11-09
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