期刊
CHEMISTRY & BIOLOGY
卷 16, 期 1, 页码 15-27出版社
CELL PRESS
DOI: 10.1016/j.chembiol.2008.11.003
关键词
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资金
- BBSRC [BBC5165281]
- A.S.N. [BBC51390X1]
- Biotechnology and Biological Sciences Research Council [BB/C516528/1] Funding Source: researchfish
- Engineering and Physical Sciences Research Council [GR/S99419/01] Funding Source: researchfish
The ability to propagate embryonic stem cells (ESCs) while maintaining their pluripotency is critical if their potential use in regenerative medicine is to be realized. The mechanisms controlling ESC self-renewal are under intense investigation, and glycogen synthase kinase 3 (GSK-3) has been implicated in regulating both self-renewal and differentiation. To clarify its role in ESCs we have used chemical genetics. We synthesized a series of bisindolylmalei-mides, a subset of which inhibit GSK-3 in murine ESCs and robustly enhance self-renewal in the presence of leukemia inhibitory factor (LIF) and serum, but not in the absence of LIF. Importantly, these molecules appear selective for GSK-3 and do not perturb other signaling pathways regulating self-renewal. Our study clarifies the functional importance of GSK-3 in regulation of ESC self-renewal and provides tools for investigating its role further.
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