A Small Molecule Primes Embryonic Stem Cells for Differentiation

The Skaggs Institute of Chemical Biology and the Department of Chemistry, The Scripps Research Institute, La Jolla, CA 92037, USA.
Cell stem cell (Impact Factor: 22.27). 06/2009; 4(5):416-26. DOI: 10.1016/j.stem.2009.04.001
Source: PubMed


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.

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    • "Author's personal copy resulting in downregulation of c-Myc, a key factor in the maintenance of ESC self-renewal (Zhu et al., 2009). Thus, Spd is dependent on the subsequent treatment with Activin A for the differentiation of Spd-primed ESC to definitive endoderm. "
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    • "As reported before, Spd has been shown to inhibit nuclear localization of nucleoside diphosphate kinase B (DNPK B), which led to the down regulation of c-MYC a known main factor in hESC self-renewal. Thus it could prime hESCs for differentiation (26). As we previously reported (27), pre-treatment of hESCs with SM suppressors of pluripotency could be a strategy to improve the efficiency of DE induction. "
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