The role of YAP transcription coactivator in regulating stem cell self-renewal and differentiation
- Ian Lian1,
- Joungmok Kim1,
- Hideki Okazawa1,
- Jiagang Zhao1,
- Bin Zhao1,
- Jindan Yu2,
- Arul Chinnaiyan3,
- Mason A. Israel4,
- Lawrence S.B. Goldstein4,
- Ramzey Abujarour5,
- Sheng Ding5 and
- Kun-Liang Guan1,6,7
- 1Moores Cancer Center, University of California at San Diego, La Jolla, California 92093, USA;
- 2Division of Hematology/Oncology, Robert H. Lurie Cancer Center, Northwestern University Feinberg Medical School, Chicago, Illinois 60611, USA;
- 3Michigan Center for Translational Pathology, University of Michigan Medical School, Ann Arbor, Michigan 48109, USA;
- 4Department of Cellular and Molecular Medicine, University of California at San Diego, La Jolla, California 92093, USA;
- 5Department of Chemistry, The Scripps Research Institute, La Jolla, California 92037, USA;
- 6Department of Pharmacology, University of California at San Diego, La Jolla, California 92093, USA
Abstract
Yes-associated protein (YAP) is a potent transcription coactivator acting via binding to the TEAD transcription factor, and plays a critical role in organ size regulation. YAP is phosphorylated and inhibited by the Lats kinase, a key component of the Hippo tumor suppressor pathway. Elevated YAP protein levels and gene amplification have been implicated in human cancer. In this study, we report that YAP is inactivated during embryonic stem (ES) cell differentiation, as indicated by decreased protein levels and increased phosphorylation. Consistently, YAP is elevated during induced pluripotent stem (iPS) cell reprogramming. YAP knockdown leads to a loss of ES cell pluripotency, while ectopic expression of YAP prevents ES cell differentiation in vitro and maintains stem cell phenotypes even under differentiation conditions. Moreover, YAP binds directly to promoters of a large number of genes known to be important for stem cells and stimulates their expression. Our observations establish a critical role of YAP in maintaining stem cell pluripotency.
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Footnotes
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↵7 Corresponding author.
E-MAIL kuguan{at}ucsd.edu; FAX (858) 534-7628.
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Article is online at http://www.genesdev.org/cgi/doi/10.1101/gad.1903310.
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Supplemental material is available at http://www.genesdev.org.
- Received January 8, 2010.
- Accepted April 12, 2010.
- Copyright © 2010 by Cold Spring Harbor Laboratory Press
