A small molecule primes embryonic stem cells for differentiation.
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Zhu, Shoutian, Wurdak, Heiko, Wang, Jian, Lyssiotis, Costas A, Peters, Eric, Cho, Charles, Wu, Xu and Schultz, Peter (2009) A small molecule primes embryonic stem cells for differentiation. Cell Stem Cell, 4 (5). pp. 416-426. ISSN 1875-9777
Abstract
Embryonic stem cells (ESCs) are an attractive source of cells for disease modeling in vitro and may eventually provide access to cells/tissues for the treatment of many degenerative diseases. However, applications of ESC-derived cell types are largely hindered by the lack of highly efficient methods for lineage-specific differentiation. Using a high-content screen, we have identified a small molecule, named stauprimide, that increases the efficiency of the directed differentiation of mouse and human ESCs in synergy with defined extracellular signaling cues. Affinity-based methods revealed that stauprimide interacts with NME2 and inhibits its nuclear localization. This, in turn, leads to downregulation of c-Myc, a key regulator of the pluripotent state. Thus, our findings identify a chemical tool that primes ESCs for efficient differentiation through a mechanism that affects c-Myc expression, and this study points to an important role for NME2 in ESC self-renewal.
| Item Type: | Article |
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| Additional Information: | author can archive post-print (ie final draft post-refereeing); Publisher's version/PDF cannot be used |
| Keywords: | STEMCELL; CHEMBIO |
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| Date Deposited: | 14 Dec 2009 13:49 |
| Last Modified: | 31 Jan 2013 00:57 |
| URI: | https://oak.novartis.com/id/eprint/1203 |