期刊
CELL STEM CELL
卷 3, 期 5, 页码 493-507出版社
CELL PRESS
DOI: 10.1016/j.stem.2008.08.017
关键词
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资金
- IGB FACS
- EMBO YIP
- EMBO Long-Term Fellowship
- Telethon Foundation
Reprogramming of nuclei allows the dedifferentiation of differentiated cells. Somatic cells can undergo epigenetic modifications and reprogramming through their fusion with embryonic stem cells (ESCs) or after overexpression of a specific blend of ESC transcription factor-encoding genes. We show here that cyclic activation of Wnt/beta-catenin signaling in ESCs with Wnt3a or the glycogen synthase kinase-3 (GSK-3) inhibitor 6-bromoindirubin-3'-oxime (BIO) strikingly enhances the ability of ESCs to reprogram somatic cells after fusion. In addition, we show that reprogramming is triggered by a dose-dependent accumulation of active beta-catenin. Reprogrammed clones express ESC-specific genes, lose somatic differentiation markers, become demethylated on Oct4 and Nanog CpG islands, and can differentiate into cardiomyocytes in vitro and generate teratomas in vivo. Our data thus demonstrate that in ESCs, periodic P-catenin accumulation via the Wnt/beta-catenin pathway provides a specific threshold that leads to the reprogramming of somatic cells after fusion.
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