Wnt/Beta-catenin/Cbp Signaling Maintains Long-term Murine Embryonic Stem Cell Pluripotency.
From: Central R&D Laboratories, Asahi Kasei Corporation, Shizuoka 416-8501, Japan. miyabayashi.tb@om.asahi-kasei.co.jp
Proceedings of the National Academy of Sciences of the United States of America
- Publish Date: Mar 2007
- ISSN: 0027-8424
- Volume: 104
- Issue: 13
- Pages: 5668-73
- Medium: Print
- Language: English
- Citation (JAMA): Miyabayashi Tomoyuki, Teo Jia-Ling, Yamamoto Masashi, et al. Wnt/Beta-catenin/Cbp Signaling Maintains Long-term Murine Embryonic Stem Cell Pluripotency.. Proc. Natl. Acad. Sci. U.S.A. Mar 2007;104:5668-73
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 Headings (Keywords): Animals, Cell Differentiation, Cells, Cultured, Culture Media, Serum-Free, Embryonic Stem Cells, Fibroblasts, Gene Expression Regulation, Membrane Proteins, Mice, Models, Biological, Phosphoproteins, Phosphorylation, Signal Transduction, Wnt Proteins, beta Catenin
Check for Full Text / PubMed Unique Identifier (PMID): 17372190
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