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A genomewide study identifies the Wnt signaling pathway as a major target of p53 in murine embryonic stem cells

  1. Author:
    Lee, K. H.
    Li, M. M.
    Michalowski, A. M.
    Zhang, X. Y.
    Liao, H. L.
    Chen, L. Y.
    Xu, Y.
    Wu, X. L.
    Huang, J.

  2. Author Address

    [Lee, Kyoung-Hwa; Li, Mangmang; Michalowski, Aleksandra M.; Zhang, Xinyue; Huang, Jing] NCI, Lab Canc Biol & Genet, Bethesda, MD 20892 USA. [Liao, Hongling; Wu, Xiaolin] NCI, Lab Mol Technol, Sci Applicat Int Corp Frederick Inc, Frederick, MD 21702 USA. [Xu, Yang] Univ Calif San Diego, Div Biol Sci, La Jolla, CA 92093 USA. [Chen, Lingyi] Nankai Univ, Coll Life Sci, Tianjin 300071, Peoples R China.;Huang, J, NCI, Lab Canc Biol & Genet, 37 Convent Dr,Room 3140, Bethesda, MD 20892 USA.;huangj3@mail.nih.gov
    1. Year: 2010
    2. Date: Jan
  2. Journal: Proceedings of the National Academy of Sciences of the United States of America
    1. 107
    2. 1
    3. Pages: 69-74
  4. Type of Article: Article
  5. ISSN: 0027-8424
  1. Abstract:

    Both p53 and the Wnt signaling pathway play important roles in regulating the differentiation of mouse embryonic stem cells (mESCs). However, it is not known whether they directly and/or functionally crosstalk in mESCs. Here we report a surprising anti-differentiation function of p53 in mESCs through directly regulating the Wnt signaling pathway. A chromatin-immunoprecipitation-based microarray (ChIP-chip) and gene expression microarray assays reveal that the Wnt signaling pathway is significantly (P value, 0.000048) overrepresented in p53-regulated genes in mESCs. The expression of five Wnt ligand genes is robustly induced by various genotoxic and nongenotoxic insults in a p53-dependent manner. Moreover, the induction of these Wnt genes is greatly attenuated in mouse embryonic fibroblast (MEF) cells and ESC-derived neural stem/progenitor cells, suggesting that the induction is mESC specific. It is established that the activation of the Wnt signaling pathway inhibits the differentiation of mESCs. Consistent with this notion, we detected an antidifferentiation activity from the conditioned medium (CM) collected from UV (UV)-treated mESCs. This antidifferentiation activity can be lowered by either the addition of Wnt antagonists into the CM or the reduction of p53 levels in UV-treated mESCs. Therefore, reminiscent of its dual functions on death and survival in somatic cells, p53 appears to regulate both prodifferentiation and antidifferentiation programs in mESCs. Our findings uncover a direct and functional connection between p53 and the Wnt signaling pathway, and expand the catalog of p53 regulated genes in mESCs.

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External Sources

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  2. DOI: 10.1073/pnas.0909734107
  3. View record in Web of Science®
  4. WOS: 000273559200013

Library Notes

  1. Fiscal Year: FY2009-2010
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