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Yap1 safeguards mouse embryonic stem cells from excessive apoptosis during differentiation

ABSTRACT: While Yap1, a Hippo pathway transcriptional effector, plays numerous roles in development and cancer, its functions in embryonic stem (ES) cell differentiation remain poorly characterized. It is known that approximately 30% of ES cells die after exiting self-renewal to differentiate, but upstream regulators of this process are not well known. We first observe that ES cells lacking Yap1 experience massive cell death upon the exit from self-renewal. We subsequently reveal that Yap1 contextually protects differentiating, but not self-renewing, mouse ES cells from hyperactivation of the apoptotic cascade. Mechanistically, Yap1 strongly activates anti-apoptotic genes via directly occupying their regulatory elements while mildly suppressing pro-apoptotic genes. Our demonstration of the pro-survival functions of Yap1 during ES cell differentiation expands our understanding of upstream regulators of the balance between survival and death during cell fate changes.

ORGANISM(S): Mus musculus

PROVIDER: GSE112606 | GEO | 2018/12/20

REPOSITORIES: GEO

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