Details

Autor(en) / Beteiligte

• Zhu, Shoutian
• Wurdak, Heiko
• Wang, Jian
• Lyssiotis, Costas A.
• Peters, Eric C.
• Cho, Charles Y.
• Wu, Xu
• Schultz, Peter G.

Titel

A Small Molecule Primes Embryonic Stem Cells for Differentiation

Ist Teil von

• Cell stem cell, 2009-05, Vol.4 (5), p.416-426

Ort / Verlag

Cambridge, MA: Elsevier Inc

Erscheinungsjahr

2009

Quelle

ScienceDirect

Beschreibungen/Notizen

• 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.