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

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.

authors

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

doi

10.1073/pnas.0701331104

subject

Has Abstract

pub_date

2007-03-27 00:00:00

pages

5668-73

issue

13

eissn

0027-8424

issn

1091-6490

pii

0701331104

journal_volume

104

pub_type

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