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A small molecule primes embryonic stem cells for differentiation.

Zhu, Shoutian and Wurdak, Heiko and Wang, Jian and Lyssiotis, Costas A and Peters, Eric and Cho, Charles and 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

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