Cytoplasmic and Nuclear TAZ Exert Distinct Functions in Regulating Primed Pluripotency.

Cytoplasmic and Nuclear TAZ Exert Distinct Functions in Regulating Primed Pluripotency.
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DOI:
10.1016/j.stemcr.2017.07.019
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发表时间:
2017-09-12
期刊:
影响因子:
5.9
通讯作者:
Ying QL
Ying QL
中科院分区:
医学1区
文献类型:
--
作者:
Zhou X;Chadarevian JP;Ruiz B;Ying QL

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小鼠上胚层干细胞(mEpiSC)和人胚胎干细胞(hESC)是致敏的多能干细胞,其自我更新可以通过细胞质稳定和β-连环蛋白的保留来维持。然而,其潜在机制在很大程度上仍然未知。在这里,我们表明,细胞质β-连环蛋白相互作用,并保留TAZ,海马通路效应,在细胞质中。TAZ的细胞质保留在核β-连环蛋白不存在的情况下促进mEpiSC自我更新,而TAZ的核易位诱导mEpiSC分化。TAZ对于幼稚小鼠胚胎干细胞(mESC)自我更新是必需的,但对于mESC向mEpiSC的适当转化是必需的。与mEpiSC一样,hESC的自我更新也可以通过β-连环蛋白和TAZ的细胞质保留来维持。我们的研究表明,TAZ如何调节细胞命运不仅取决于细胞类型,而且还取决于其亚细胞定位。TAZ是细胞质β-catenin的结合伴侣TAZ是mESCs向mEpiSCs转化所必需的TAZ的细胞质滞留促进mEpiSC和hESC自我更新TAZ的核转位诱导mEpiSC和hESC分化在这篇文章中,Qi-Long Ying和同事表明,细胞质β-catenin相互作用并将TAZ保留在mEpiSC和hESC的细胞质中。TAZ的胞质滞留在核β-连环蛋白不存在的情况下促进mEpiSC和hESC自我更新,而TAZ的核易位诱导mEpiSC和hESC分化。这项研究表明,转录辅激活因子也可以发挥功能的作用,在细胞质中。
Mouse epiblast stem cells (mEpiSCs) and human embryonic stem cells (hESCs) are primed pluripotent stem cells whose self-renewal can be maintained through cytoplasmic stabilization and retention of β-catenin. The underlying mechanism, however, remains largely unknown. Here, we show that cytoplasmic β-catenin interacts with and retains TAZ, a Hippo pathway effector, in the cytoplasm. Cytoplasmic retention of TAZ promotes mEpiSC self-renewal in the absence of nuclear β-catenin, whereas nuclear translocation of TAZ induces mEpiSC differentiation. TAZ is dispensable for naive mouse embryonic stem cell (mESC) self-renewal but required for the proper conversion of mESCs to mEpiSCs. The self-renewal of hESCs, like that of mEpiSCs, can also be maintained through the cytoplasmic retention of β-catenin and TAZ. Our study indicates that how TAZ regulates cell fate depends on not only the cell type but also its subcellular localization. TAZ is a binding partner of cytoplasmic β-catenin TAZ is essential for the conversion of mESCs to mEpiSCs Cytoplasmic retention of TAZ promotes mEpiSC and hESC self-renewal Nuclear translocation of TAZ induces mEpiSC and hESC differentiation In this article, Qi-Long Ying and colleagues show that cytoplasmic β-catenin interacts and retains TAZ in the cytoplasm in mEpiSCs and hESCs. Cytoplasmic retention of TAZ promotes mEpiSC and hESC self-renewal in the absence of nuclear β-catenin, whereas nuclear translocation of TAZ induces mEpiSC and hESC differentiation. This study demonstrates that transcriptional co-activators can also exert functional roles in the cytoplasm.
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