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PMID: 17372190 Published · ppublish English Journal Article

Wnt/beta-catenin/CBP signaling maintains long-term murine embryonic stem cell pluripotency.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 104 ·No. 13 ·2007-03-27 ·Pages 5668-73

Miyabayashi T, Teo JL, Yamamoto M, McMillan M, Nguyen C, Kahn M

Abstract

Embryonic stem cells (ESCs) represent an important research tool and a potential resource for regenerative medicine. Generally, ESCs are cocultured with a supportive feeder cell layer of murine embryonic fibroblasts, which maintain the ESCs' capacity for self-renewal and block spontaneous differentiation. These cumbersome conditions, as well as the risk of xenobiotic contamination of human ESCs grown on murine embryonic fibroblasts, make it a priority to develop chemically defined methods that can be safely used for the expansion of ESCs. Using a high-throughput, cell-based assay, we identified the small molecule IQ-1 that allows for the Wnt/beta-catenin-driven long-term expansion of mouse ESCs and prevents spontaneous differentiation. We demonstrate that IQ-1, by targeting the PR72/130 subunit of the serine/threonine phosphatase PP2A, prevents beta-catenin from switching coactivator usage from CBP to p300. The increase in beta-catenin/CBP-mediated transcription at the expense of beta-catenin/p300-mediated transcription is critical for the maintenance of murine stem cell pluripotency.

MeSH Terms
Animals Cell Differentiation Cells, Cultured Culture Media, Serum-Free/pharmacology Embryonic Stem Cells/metabolism Fibroblasts/metabolism Gene Expression Regulation Membrane Proteins/metabolism Mice Models, Biological Phosphoproteins/metabolism Phosphorylation Signal Transduction Wnt Proteins/metabolism beta Catenin/metabolism
Chemicals
Culture Media, Serum-Free Membrane Proteins Pag1 protein, mouse Phosphoproteins Wnt Proteins beta Catenin
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Miyabayashi Tomoyuki
Central R&D Laboratories, Asahi Kasei Corporation, Shizuoka 416-8501, Japan. miyabayashi.tb@om.asahi-kasei.co.jp
Teo Jia-Ling
Yamamoto Masashi
McMillan Michael
Nguyen Cu
Kahn Michael
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.0701331104
Email
miyabayashi.tb@om.asahi-kasei.co.jp
Published
2007-03-27
Epub
2007-00-19
Pages
5668-73
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC1838514
Subset
IM
External Links
PubMed source DOI: 10.1073/pnas.0701331104 PMC Full Text View journal details
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