The p53 family coordinates Wnt and nodal inputs in mesendodermal differentiation of embryonic stem cells Journal Article


Authors: Wang, Q.; Zou, Y.; Nowotschin, S.; Kim, S. Y.; Li, Q. V.; Soh, C. L.; Su, J.; Zhang, C.; Shu, W.; Xi, Q.; Huangfu, D.; Hadjantonakis, A. K.; Massagué, J.
Article Title: The p53 family coordinates Wnt and nodal inputs in mesendodermal differentiation of embryonic stem cells
Abstract: In this study, we outline a regulatory network that involves the p53 tumor suppressor family and the Wnt pathway acting together with the TGF-β pathway in mesendodermal differentiation of mouse and human embryonic stem cells. Knockout of all three members, p53, p63, and p73, shows that the p53 family is essential for mesendoderm specification during exit from pluripotency in embryos and in culture. Wnt3 and its receptor Fzd1 are direct p53 family target genes in this context, and induction of Wnt signaling by p53 is critical for activation of mesendodermal differentiation genes. Globally, Wnt3-activated Tcf3 and nodal-activated Smad2/3 transcription factors depend on each other for co-occupancy of target enhancers associated with key differentiation loci. Our results therefore highlight an unanticipated role for p53 family proteins in a regulatory network that integrates essential Wnt-Tcf and nodal-Smad inputs in a selective and interdependent way to drive mesendodermal differentiation of pluripotent cells. © 2017 Elsevier Inc.
Keywords: transcription; embryonic stem cells; wnt; smad; tgf-β; tcf; mesendoderm differentiation; p53 tumor suppressor
Journal Title: Cell Stem Cell
Volume: 20
Issue: 1
ISSN: 1934-5909
Publisher: Cell Press  
Date Published: 2017-01-05
Start Page: 70
End Page: 86
Language: English
DOI: 10.1016/j.stem.2016.10.002
PROVIDER: scopus
PMCID: PMC5218926
PUBMED: 27889317
DOI/URL:
Notes: Article -- Export Date: 2 February 2017 -- Source: Scopus
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MSK Authors
  1. Joan Massague
    285 Massague
  2. Weiping Shu
    16 Shu
  3. Danwei Huangfu
    28 Huangfu
  4. Qiaoran Xi
    8 Xi
  5. Qing Li
    6 Li
  6. Yilong Zou
    13 Zou
  7. Jie   Su
    5 Su
  8. Chew-Li   Soh
    6 Soh
  9. Qiong   Wang
    3 Wang