Involvement of GSK-3 in regulation of murine embryonic stem cell self-renewal revealed by a series of bisindolylmaleimides
Bone, H. K., Damiano, T., Bartlett, S., Perry, A., Letchford, J., Ripoli, Y. S., Nelson, A. S. and Welham, M. J., 2009. Involvement of GSK-3 in regulation of murine embryonic stem cell self-renewal revealed by a series of bisindolylmaleimides. Chemistry & Biology, 16 (1), pp. 15-27.
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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.
|Creators||Bone, H. K., Damiano, T., Bartlett, S., Perry, A., Letchford, J., Ripoli, Y. S., Nelson, A. S. and Welham, M. J.|
|Departments||Faculty of Science > Pharmacy & Pharmacology|
|Research Centres||Centre for Regenerative Medicine|
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