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EMBO Rep. 2016 Apr;17(4):519-29. doi: 10.15252/embr.201540933. Epub 2016 Feb 25.

Yap1 is dispensable for self-renewal but required for proper differentiation of mouse embryonic stem (ES) cells.

Author information

1
Department of Molecular Biosciences, Institute for Cellular and Molecular Biology, Center for Systems and Synthetic Biology, The University of Texas at Austin, Austin, TX, USA.
2
Department of Molecular Biosciences, Institute for Cellular and Molecular Biology, Center for Systems and Synthetic Biology, The University of Texas at Austin, Austin, TX, USA jonghwankim@mail.utexas.edu.

Abstract

Yap1 is a transcriptional co-activator of the Hippo pathway. The importance of Yap1 in early cell fate decision during embryogenesis has been well established, though its role in embryonic stem (ES) cells remains elusive. Here, we report that Yap1 plays crucial roles in normal differentiation rather than self-renewal of ES cells. Yap1-depleted ES cells maintain undifferentiated state with a typical colony morphology as well as robust alkaline phosphatase activity. These cells also retain comparable levels of the core pluripotent factors, such as Pou5f1 and Sox2, to the levels in wild-type ES cells without significant alteration of lineage-specific marker genes. Conversely, overexpression of Yap1 in ES cells promotes nuclear translocation of Yap1, resulting in disruption of self-renewal and triggering differentiation by up-regulating lineage-specific genes. Moreover, Yap1-deficient ES cells show impaired induction of lineage markers during differentiation. Collectively, our data demonstrate that Yap1 is a required factor for proper differentiation of mouse ES cells, while remaining dispensable for self-renewal.

KEYWORDS:

Hippo pathway; Yap1; differentiation; embryonic stem cells; self‐renewal

PMID:
26917425
PMCID:
PMC4818770
DOI:
10.15252/embr.201540933
[Indexed for MEDLINE]
Free PMC Article

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