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

机译:单向胚胎的单细胞转录组分析揭示了对人类预体发育的父母的影响

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摘要

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.
机译:为了研究亲本基因组对早期胚胎发生的贡献,我们系统地分析了从1细胞到桑椹胚阶段的人类双亲和单亲胚胎的单细胞转录组。我们观察到单亲胚胎表现出可变的和降低的胚胎基因组激活(EGA)。比较转录组分析发现,在着床前阶段,807个母系偏向表达基因(MBG)和581个父系偏向表达基因(PBG)。MBGs在4-细胞阶段变得明显,并有助于EGA的启动,而PBGs优先出现在8-细胞阶段,可能会影响胚胎压实和滋养外胚层规格。调控网络分析显示,DUX4、EGR2和DUXA是MBGs表达的关键转录因子;ZNF263和KLF3对PBGs的表达很重要。我们证明了父母特异性DNA甲基化可能是大多数PBG表达的原因。我们的结果为理解亲本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本起源效应。

著录项

  • 来源
    《Cell stem cell》 |2019年第5期|共22页
  • 作者单位

    Cent S Univ Sch Basic Med Sci Inst Reprod &

    Stem Cell Engn Changsha 410078 Hunan Peoples R;

    Chinese Acad Med Sci Ctr Syst Med Inst Basic Med Sci Beijing 100005 Peoples R China;

    BGI Shenzhen Shenzhen 518083 Peoples R China;

    Cent S Univ Sch Basic Med Sci Inst Reprod &

    Stem Cell Engn Changsha 410078 Hunan Peoples R;

    BGI Shenzhen Shenzhen 518083 Peoples R China;

    Reprod &

    Genet Hosp CITIC Xiangya Changsha 410078 Hunan Peoples R China;

    Chinese Acad Med Sci Ctr Syst Med Inst Basic Med Sci Beijing 100005 Peoples R China;

    BGI Shenzhen Shenzhen 518083 Peoples R China;

    BGI Shenzhen Shenzhen 518083 Peoples R China;

    BGI Shenzhen Shenzhen 518083 Peoples R China;

    BGI Shenzhen Shenzhen 518083 Peoples R China;

    BGI Shenzhen Shenzhen 518083 Peoples R China;

    Cent S Univ Sch Basic Med Sci Inst Reprod &

    Stem Cell Engn Changsha 410078 Hunan Peoples R;

    Chinese Acad Med Sci Ctr Syst Med Inst Basic Med Sci Beijing 100005 Peoples R China;

    BGI Shenzhen Shenzhen 518083 Peoples R China;

    Cent S Univ Sch Basic Med Sci Inst Reprod &

    Stem Cell Engn Changsha 410078 Hunan Peoples R;

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  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 细胞生物学;
  • 关键词

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