Transcriptomics,Genomics

Dataset Information

17

P53 regulates the Wnt signaling pathway in murine embryonic stem cells


ABSTRACT: Genome-wide analysis of gene expression changes in murine embryonic stem cells (R1E cells) treated with Ultraviolet and adriamycin Both p53 and the Wnt signaling pathways play important roles in tumorigenesis and development. However, few studies, particularly on a genome-wide scale, have linked these two pathways. Here we show that p53 directly regulates the Wnt signaling pathway in murine embryonic stem cells (mESCs) using an integrated genome-wide approach. A chromatin-immunoprecipitation-based microarray assay (ChIP-chip) reveals that the Wnt signaling pathway is significantly over-represented in p53 bound genes. Using gene expression microarray and real-time PCR, we demonstrate that the expressions of many Wnts are robustly induced by various stresses, including DNA damage and hypoxia that activate p53. Importantly, the activation of p53 is a prerequisite for the induction of Wnts. Moreover, conditional medium (CM) collected from ultraviolet (UV)-treated mESCs contains an anti-differentiation activity, which can be lowered by either the addition of Wnt signaling inhibitors into the CM or the reduction of p53 levels in UV-treated mESCs. These results suggest that stressed mESCs utilize the p53-Wnt signaling axis to signal neighboring mESCs to delay the differentiation. Together, our results uncover a novel connection between p53 and the Wnt signaling pathways in mediating cell-to-cell communication in mESCs, and provide insights into the functions of these two pathways in tumorigenesis and development. Overall design: We analyzed R1E cells treated with mock (control), adriamycin or Ultraviolet using Affymetrix Mouse Gene ST 1.0 arrays. Four replicates for each treatment were performed.

INSTRUMENT(S): [MoGene-1_0-st] Affymetrix Mouse Gene 1.0 ST Array [transcript (gene) version]

SUBMITTER: Jing Huang   

PROVIDER: GSE16428 | GEO | 2010-01-19

SECONDARY ACCESSION(S): PRJNA116375

REPOSITORIES: GEO

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Publications

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

Lee Kyoung-Hwa KH   Li Mangmang M   Michalowski Aleksandra M AM   Zhang Xinyue X   Liao Hongling H   Chen Lingyi L   Xu Yang Y   Wu Xiaolin X   Huang Jing J  

Proceedings of the National Academy of Sciences of the United States of America 20091214 1


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 antidifferentiation 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 significantl  ...[more]

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