Snail1-dependent control of embryonic stem cell pluripotency and lineage commitment.

Snail1-dependent control of embryonic stem cell pluripotency and lineage commitment.
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DOI:
10.1038/ncomms4070
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发表时间:
2014
影响因子:
16.6
通讯作者:
Weiss, Stephen J.
Weiss, Stephen J.
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Lin, Yongshun;Li, Xiao-Yan;Willis, Amanda L.;Liu, Chengyu;Chen, Guokai;Weiss, Stephen J.

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胚胎干细胞(ESCs)具有自我更新和多能性的双重特性,以及分化为所有三个胚层的能力。Wnt家族成员可以促进ESC的维持和触发分化,同时还控制Snail 1(一种锌指转录抑制因子)的表达。Snail 1与从细胞周期调节和细胞存活到上皮-间充质转化(EMT)和原肠胚形成的事件有关,但其在ESCs自我更新、多能性或谱系定型中的作用仍不明确。在这里,我们证明了使用条件性敲除小鼠胚胎干细胞的同基因对,蜗牛1发挥Wnt和EMT的独立控制干细胞转录组,而不影响自我更新或多能性相关的功能。相比之下,在ESC分化过程中,内源性Wnt介导的Snail 1表达的爆发调节神经外胚层的命运,同时在上胚层干细胞退出和随后的谱系命运决定中发挥所需的作用,定义中胚层的承诺。
Embryonic stem cells (ESCs) exhibit the dual properties of self-renewal and pluripotency as well as the ability to undergo differentiation that gives rise to all three germ layers. Wnt family members can both promote ESC maintenance and trigger differentiation while also controlling the expression of Snail1, a zinc-finger transcriptional repressor. Snail1 has been linked to events ranging from cell cycle regulation and cell survival to epithelial–mesenchymal transition (EMT) and gastrulation, but its role in self-renewal, pluripotency or lineage commitment in ESCs remains undefined. Here we demonstrate using isogenic pairs of conditional knockout mouse ESCs, that Snail1 exerts Wnt- and EMT independent control over the stem cell transcriptome without affecting self-renewal or pluripotency-associated functions. By contrast, during ESC differentiation, an endogenous Wnt-mediated burst in Snail1 expression regulates neuroectodermal fate while playing a required role in epiblast stem cell exit and the consequent lineage fate decisions that define mesoderm commitment.
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