A Small Molecule Primes Embryonic Stem Cells for Differentiation

作者：Zhu Shoutian; Wurdak Heiko; Wang Jian; Lyssiotis Costas A; Peters Eric C; Cho Charles Y; Wu Xu^*; Schultz Peter G

来源：Cell Stem Cell, 2009, 4(5): 416-426.

DOI：10.1016/j.stem.2009.04.001

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.

• 出版日期2009-5-8