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- LATS-YAP/TAZ controls lineage specification by regulating TGFβ signaling and Hnf4α expression during liver development
- D H Lee; J O Park; T S Kim; S K Kim; T H Kim; M C Kim; G S Park; Jeong Hwan Kim; S Kuninaka; E N Olson; H Saya; Seon-Young Kim; H Lee; D S Lim
- Bibliographic Citation
- Nature Communications, vol. 7, pp. 11961-11961
- Publication Year
- The Hippo pathway regulates the self-renewal and differentiation of various adult stem cells,
but its role in cell fate determination and differentiation during liver development remains
unclear. Here we report that the Hippo pathway controls liver cell lineage specification and
proliferation separately from Notch signalling, using mice and primary hepatoblasts with
liver-specific knockout of Lats1 and Lats2 kinase, the direct upstream regulators of YAP and
TAZ. During and after liver development, the activation of YAP/TAZ induced by loss of Lats1/
2 forces hepatoblasts or hepatocytes to commit to the biliary epithelial cell (BEC) lineage. It
increases BEC and fibroblast proliferation by up-regulating TGFb signalling, but suppresses
hepatoblast to hepatocyte differentiation by repressing Hnf4a expression. Notably, oncogenic
YAP/TAZ activation in hepatocytes induces massive p53-dependent cell senescence/death.
Together, our results reveal that YAP/TAZ activity levels govern liver cell differentiation and
proliferation in a context-dependent manner.
- Springer-Nature Pub Group
- Appears in Collections:
- Aging Convergence Research Center > 1. Journal Articles
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