Abstract
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.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Adaptor Proteins, Signal Transducing / metabolism
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Aneuploidy
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Animals
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Cell Cycle Proteins
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Cell Differentiation / genetics*
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Cells, Cultured
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Embryonic Stem Cells / cytology
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Embryonic Stem Cells / metabolism*
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Hepatocytes / cytology
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Hippo Signaling Pathway
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Mice
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Mice, Inbred C57BL
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Phosphoproteins / metabolism
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Protein Serine-Threonine Kinases / deficiency
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Protein Serine-Threonine Kinases / genetics
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Protein Serine-Threonine Kinases / metabolism*
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Signal Transduction
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Transcription Factors / metabolism
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Tumor Suppressor Protein p53 / metabolism
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Tumor Suppressor Proteins / deficiency
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Tumor Suppressor Proteins / genetics
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Tumor Suppressor Proteins / metabolism*
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YAP-Signaling Proteins
Substances
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Adaptor Proteins, Signal Transducing
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Cell Cycle Proteins
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Phosphoproteins
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Transcription Factors
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Tumor Suppressor Protein p53
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Tumor Suppressor Proteins
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YAP-Signaling Proteins
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Yap1 protein, mouse
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LATS2 protein, mouse
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Protein Serine-Threonine Kinases