A Small Molecule Primes Embryonic Stem Cells for Differentiation

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...

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Published inCell stem cell Vol. 4; no. 5; pp. 416 - 426
Main Authors Zhu, Shoutian, Wurdak, Heiko, Wang, Jian, Lyssiotis, Costas A., Peters, Eric C., Cho, Charles Y., Wu, Xu, Schultz, Peter G.
Format Journal Article
LanguageEnglish
Published Cambridge, MA Elsevier Inc 08.05.2009
Cell Press
Subjects
Animals
Biological and medical sciences
Cell Differentiation - drug effects
Cell differentiation, maturation, development, hematopoiesis
Cell physiology
CHEMBIO
Chromatin Immunoprecipitation
Down-Regulation
Embryo, Mammalian - cytology
Embryo, Mammalian - metabolism
Embryonic Stem Cells - cytology
Embryonic Stem Cells - drug effects
Embryonic Stem Cells - metabolism
Endoderm - metabolism
Enzyme Inhibitors - pharmacology
Fundamental and applied biological sciences. Psychology
Genes, myc
Humans
Mice
Molecular and cellular biology
NM23 Nucleoside Diphosphate Kinases - antagonists & inhibitors
NM23 Nucleoside Diphosphate Kinases - genetics
NM23 Nucleoside Diphosphate Kinases - metabolism
Staurosporine - analogs & derivatives
Staurosporine - pharmacology
STEMCELL
STEMCELL
CHEMBIO
Vertebrata
Mammalia
Mouse
Embryonic cell
Stem cell
Rodentia
Small molecule
Cell differentiation
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Summary: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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ISSN:1934-5909
1875-9777
DOI:10.1016/j.stem.2009.04.001