Cdk1 interplays with Oct4 to repress differentiation of embryonic stem cells into trophectoderm

Cdk1 interplays with Oct4 to repress differentiation of embryonic stem cells into trophectoderm
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Cdk1与Oct4相互作用抑制胚胎干细胞分化为滋养外胚层

DOI:
10.1016/j.febslet.2012.10.030
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发表时间:
2012-11-30
期刊:
影响因子:
3.5
通讯作者:
Zhang, Weiwei
Zhang, Weiwei
中科院分区:
生物学3区
文献类型:
--
作者:
Li, Lei;Wang, Juanjuan;Zhang, Weiwei

文献摘要

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CDK1在未分化的ES细胞中发挥重要作用,但其机制尚不清楚。本研究探讨了CDK1如何与Oct4协同抑制小鼠ES细胞的分化。我们发现了CDK1和Oct4之间的直接相互作用,而其他CDK成员,包括CDK2和CDK4,未能与Oct4结合。通过免疫细胞化学,我们发现CDK1和Oct4共定位于ES细胞。并对CDK1-Oct4复合体的生物学功能进行了探讨。我们发现,CDK1增强了Oct4与滋养外胚层标记CDx2的结合,并促进了CDx2的抑制。这种调节不依赖于细胞周期蛋白和CDK1的激酶活性。我们的研究解释了CDK1和Oct4如何相互作用来抑制ES细胞分化为滋养外胚层,从而维持茎。
Cdk1 plays an important role in undifferentiated ES cells, but the underlying mechanism remains unclear. This study explores how Cdk1 collaborates with Oct4 to inhibit differentiation in mouse ES cells. We show a direct interaction between Cdk1 and Oct4, whereas other Cdk members, including Cdk2 and Cdk4, fail to associate with Oct4. By immunocytochemistry we show that Cdk1 and Oct4 co-localize in ES cells. The biological function of the Cdk1-Oct4 complex was also addressed. We found that Cdk1 enhances the binding of Oct4 on the trophectoderm marker Cdx2 and promotes Cdx2 repression. This regulation is independent of Cyclins and of the kinase activity of Cdk1. Our study explains how Cdk1 and Oct4 interplay to inhibit ES cell differentiation into trophectoderm and thereby maintain stemness.