Single-Cell RNA-Seq Reveals Cellular Heterogeneity of Pluripotency Transition and X Chromosome Dynamics during Early Mouse Development
Single-Cell RNA-Seq Reveals Cellular Heterogeneity of Pluripotency Transition and X Chromosome Dynamics during Early Mouse Development
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DOI：
10.1016/j.celrep.2019.02.031
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发表时间：
2019-03-05
期刊：
影响因子：
8.8
通讯作者：
Deng, Qiaolin
中科院分区：
文献类型：
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作者：
Cheng, Shangli;Pei, Yu;Deng, Qiaolin
胚胎着床后，外胚层(EPI)细胞从原始的多能细胞过渡到多能细胞，并伴随着女性X染色体活性的动态变化。为了研究这一过程的分子属性，我们对E5.25、E5.5、E6.25和E6.5小鼠胚胎的1,724个细胞进行了单细胞RNA-SEQ分析。我们在EPI细胞中发现了三种细胞状态，它们捕捉到了沿着多潜能连续体的转变和原始条纹倾向的获得。三种EPI状态的转换是由内脏内胚层(VE)发出的诱导信号活动驱动的。在雌性胚胎的EPI中，X染色体再激活(XCR)是在印记X染色体失活(XCI)完成之前启动的，随之而来的随机XCI是高度不同步的。此外，印记父系XCI在VE中的进展速度快于胚外外胚层。我们的研究提供了原肠形成前紧急线龄承诺的详细分子路线图，并表征了小鼠早期发育过程中的X染色体动力学。
Following implantation, the epiblast (EPI) cells transit from the naive to primed pluripotency, accompanied by dynamic changes in X chromosome activity in females. To investigate the molecular attributes of this process, we performed single-cell RNA-seq analysis of 1,724 cells of E5.25, E5.5, E6.25, and E6.5 mouse embryos. We identified three cellular states in the EPI cells that capture the transition along the pluripotency continuum and the acquisition of primitive streak propensity. The transition of three EPI states was driven by inductive signaling activity emanating from the visceral endoderm (VE). In the EPI of female embryos, X chromosome reactivation (XCR) was initiated prior to the completion of imprinted X chromosome inactivation (XCI), and the ensuing random XCI was highly asynchronous. Moreover, imprinted paternal XCI proceeded faster in the VE than the extraembryonic ectoderm. Our study has provided a detailed molecular roadmap of the emergent line-age commitment before gastrulation and characterized X chromosome dynamics during early mouse development.