Journal
CELL DEATH AND DIFFERENTIATION
Volume 21, Issue 4, Pages 624-633Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/cdd.2013.188
Keywords
Hippo; p53; stem cells; Yap; bivalent chromatin; Lats2
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Funding
- Dr. Miriam and Sheldon G Adelson Medical Research Foundation
- Israel Cancer Association
- National Cancer Institute [R37 CA40099]
- Israel Science Foundation (ISF) [1779/11]
- Flight Attendant Medical Research Institute (FAMRI)
- Lower Saxony-Israeli Association
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Differentiation is a highly controlled process essential for embryonic and adult development. Moreover, disruption of proper differentiation is often associated with human diseases, including cancer. We analyzed the involvement of the tumor-suppressor Lats2 in mouse embryonic stem cell (mESC) pluripotency and differentiation, and report that mESCs lacking Lats2 are unable to sustain stemness and are not able to initiate and coordinate developmental transcriptional programs. Lats2 -/- mESCs retain bivalent 'poised' chromatin marks on developmental genes and exhibit germ layer ambiguity both in vitro and in vivo. Importantly, in coordinating proper germ layer specification, Lats2 engages in a feedback loop with another tumor suppressor, p53.
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