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Cell:个体发育始于四细胞胚胎时期

 个体发育始于何时?在受孕第二天胚胎只有四个细胞的时候就开始成形了,这个研究成为了Cell的封面文章。尽管细胞看上去一模一样,但研究人员通过测序检测单细胞水平上的基因活性后发现:四细胞胚胎阶段这些细胞就已经各不相同了:一些基因活性存在着明显差异,而多能性网络中的一部分:Sox2基因差异最大。Sox2活性减弱会引导细胞发展为胎盘的主调控子活性增加。在四细胞阶段,Oct4 和Sox2 的靶蛋白,比如Sox21,具有高度的异质性,敲除Sox21后Cdx的表达上调,这个阶段的细胞未来命运就已经被决定了。

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参阅文献:
Heterogeneity in Oct4 and Sox2 Targets Biases Cell Fate in 4-Cell Mouse Embryos.
Cell. 2016 Mar 24;61-74. pii:S0092-8674(16)30061-7. doi:10.1016/j.cell.2016.01.047.
The major and essential objective of pre-implantation development is to establish embryonic and extra-embryonic cell fates. To address when and how this fundamental process is initiated in mammals, we characterize transcriptomes of all individual cells throughout mouse pre-implantation development. This identifies targets of master pluripotency regulators Oct4 and Sox2 as being highly heterogeneously expressed between blastomeres of the 4-cell embryo, with Sox21 showing one of the most heterogeneous expression profiles. Live-cell tracking demonstrates that cells with decreased Sox21 yield more extra-embryonic than pluripotent progeny. Consistently, decreasing Sox21results in premature upregulation of the differentiation regulator Cdx2, suggesting that Sox21 helps safeguard pluripotency. Furthermore,Sox21 is elevated following increased expression of the histone H3R26-methylase CARM1 and is lowered following CARM1 inhibition, indicating the importance of epigenetic regulation. Therefore, our results indicate that heterogeneous gene expression, as early as the 4-cell stage, initiates cell-fate decisions by modulating the balance of pluripotency and differentiation.
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