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Genetic programs in human and mouse early embryos revealed by single-cell RNA sequencing

机译：单细胞RNA测序揭示人和小鼠早期胚胎的遗传程序

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摘要

Mammalian pre-implantation development is a complex process involving dramatic changes in the transcriptional architecture. We report here a comprehensive analysis of transcriptome dynamics from oocyte to morula in both human and mouse embryos, using single-cell RNA sequencing. Based on single-nucleotide variants in human blastomere messenger RNAs and paternal-specific single-nucleotide polymorphisms, we identify novel stage-specific mono-allelic expression patterns for a significant portion of polymorphic gene transcripts (25 to 53%). By weighted gene co-expression network analysis, we find that each developmental stage can be delineated concisely by a small number of functional modules of co-expressed genes. This result indicates a sequential order of transcriptional changes in pathways of cell cycle, gene regulation, translation and metabolism, acting in a step-wise fashion from cleavage to morula. Cross-species comparisons with mouse pre-implantation embryos reveal that the majority of human stage-specific modules (7 out of 9) are notably preserved, but developmental specificity and timing differ between human and mouse. Furthermore, we identify conserved key members (or hub genes) of the human and mouse networks. These genes represent novel candidates that are likely to be key in driving mammalian pre-implantation development. Together, the results provide a valuable resource to dissect gene regulatory mechanisms underlying progressive development of early mammalian embryos.
机译：哺乳动物的植入前发育是一个复杂的过程，涉及转录结构的巨大变化。我们在此报告使用单细胞RNA测序对人类和小鼠胚胎中从卵母细胞到桑子的转录组动力学的全面分析。基于人类卵裂球信使RNA中的单核苷酸变体和父本特异性单核苷酸多态性，我们确定了相当一部分多态性基因转录本的新型阶段特异性单等位基因表达模式（25％至53％）。通过加权基因共表达网络分析，我们发现每个发育阶段可以由少数几个共表达基因的功能模块简明地描绘。该结果表明细胞周期，基因调节，翻译和代谢途径中转录变化的顺序顺序，以从切割到桑from的逐步方式起作用。与小鼠植入前胚胎的种间比较显示，大多数人类阶段特异性模块（9个中的7个）均得到了保留，但是人与小鼠之间的发育特异性和时机不同。此外，我们确定了人类和小鼠网络的保守关键成员（或中心基因）。这些基因代表了可能在推动哺乳动物植入前发育中发挥关键作用的新候选物。在一起，结果提供了宝贵的资源，以剖析早期哺乳动物胚胎逐步发展的基因调控机制。

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  • 来源
    《Nature》 |2013年第7464期|593-597|共5页
  • 作者

    Zhigang Xue; Kevin Huang; Chaochao Cai; Lingbo Cai; Chun-yan Jiang; Yun Feng; Zhenshan Liu; Qiao Zeng; Liming Cheng; Yi E. Sun; Jia-yin Liu; Steve Horvath; Guoping Fan;

  • 作者单位

    Translational CenterforStem Cell Research,Tongji Hospital, Department of Regenerative Medicine,Tongji University School of Medicine, Shanghai 200065, China;

    Department of Human Genetics, David Geffen School of Medicine, UCLA, Los Angeles, California 90095, USA;

    Department of Human Genetics, David Geffen School of Medicine, UCLA, Los Angeles, California 90095, USA;

    State Key Laboratory of Reproductive Medicine, Center of Clinical Reproductive Medicine, First Affiliated Hospital, Nanjing Medical University, Nanjing 210029, China;

    State Key Laboratory of Reproductive Medicine, Center of Clinical Reproductive Medicine, First Affiliated Hospital, Nanjing Medical University, Nanjing 210029, China;

    Translational CenterforStem Cell Research,Tongji Hospital, Department of Regenerative Medicine,Tongji University School of Medicine, Shanghai 200065, China;

    Translational CenterforStem Cell Research,Tongji Hospital, Department of Regenerative Medicine,Tongji University School of Medicine, Shanghai 200065, China;

    Translational CenterforStem Cell Research,Tongji Hospital, Department of Regenerative Medicine,Tongji University School of Medicine, Shanghai 200065, China;

    Translational CenterforStem Cell Research,Tongji Hospital, Department of Regenerative Medicine,Tongji University School of Medicine, Shanghai 200065, China;

    Translational CenterforStem Cell Research,Tongji Hospital, Department of Regenerative Medicine,Tongji University School of Medicine, Shanghai 200065, China;

    State Key Laboratory of Reproductive Medicine, Center of Clinical Reproductive Medicine, First Affiliated Hospital, Nanjing Medical University, Nanjing 210029, China;

    Department of Human Genetics, David Geffen School of Medicine, UCLA, Los Angeles, California 90095, USA;

    Department of Human Genetics, David Geffen School of Medicine, UCLA, Los Angeles, California 90095, USA;

  • 收录信息 美国《科学引文索引》(SCI);美国《工程索引》(EI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
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