Cytoplasmic and Nuclear TAZ Exert Distinct Functions in Regulating Primed Pluripotency

5 years ago

Cytoplasmic and Nuclear TAZ Exert Distinct Functions in Regulating Primed Pluripotency

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.

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Teaser

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.

Publisher URL: www.sciencedirect.com/science

DOI: S2213671117303296