Cell:受精卵发育第二天,胚胎细胞分化就已经出现差异
2016/03/28
当精子和卵子在输卵管中相遇后,经历受精过程形成受精卵,预示着一个新生命开始启程。近期,发表在《Cell》上的一篇最新研究文章揭示,早在4细胞胚胎阶段,细胞内的基因表达就已经出现差异。


当精子和卵子在输卵管中相遇后,经历受精过程形成受精卵,预示着一个新生命开始启程。受精卵会在输卵管内经过多次有丝分裂形成由多个全能型干细胞组成的细胞团,并逐步转入子宫,在子宫腔内完成后续发育。随后,胚胎干细胞会失去全能性,朝着多能性方向发展。

但是,细胞出现差异性分化的时间点一直未知。近期,发表在《Cell》上的一篇最新研究文章揭示,早在4细胞胚胎阶段,细胞内的基因表达就已经出现差异。

受精卵发育第二天,胚胎细胞就已经定好了“方向”

这一最新研究结果由来自于剑桥大学和欧洲生物信息研究所(EMBL-EBI)的研究团队完成。他们以老鼠早期胚胎(植入前)为研究模型,利用最先进测序技术,分析了每个单细胞的转录组差异。

结果显示,在4细胞胚胎阶段,各细胞内基因表达模式就已经存在差异。其中,调控胚胎干细胞多能性和自我更新功能的关键基因Oct4和Sox2的下游基因Sox21的表达差异尤为突出。当Sox21基因表达活性降低后,调控细胞发育成胎盘的下游基因网络将会被激活。

文章作者、剑桥大学生理学、神经学发育教授Magdalena Zernicka-Goetz 表示,生命始于受精卵,但是调控细胞多能性和分化的平衡,以启动各细胞出现不同分化的关键时间点却一直没有被研究清晰。借助该研究成果我们知道,即便是受精卵开始发育的第二天,即4细胞胚胎阶段,细胞就已经“规划”好了分化方向。

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  • Heterogeneity in Oct4 and Sox2 Targets Biases Cell Fate in 4-Cell Mouse Embryos

    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 Sox21 results 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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