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A small molecule primes embryonic stem cells for differentiation

Academic Article
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Overview

related to degree

  • Lyssiotis, Costas A, Ph.D. in Chemical Biology, Scripps Research 2005 - 2010

authors

  • Zhu, S.
  • Wurdak, H.
  • Wang, J.
  • Lyssiotis, Costas A
  • Peters, E. C.
  • Cho, C. Y.
  • Wu, Xu
  • Schultz, Peter

publication date

  • May 2009

journal

  • Cell Stem Cell  Journal

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.

subject areas

  • Animals
  • Cell Differentiation
  • Chromatin Immunoprecipitation
  • Down-Regulation
  • Embryo, Mammalian
  • Embryonic Stem Cells
  • Endoderm
  • Enzyme Inhibitors
  • Genes, myc
  • Humans
  • Mice
  • NM23 Nucleoside Diphosphate Kinases
  • Staurosporine
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Identity

International Standard Serial Number (ISSN)

  • 1934-5909

Digital Object Identifier (DOI)

  • 10.1016/j.stem.2009.04.001

PubMed ID

  • 19427291
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Additional Document Info

start page

  • 416

end page

  • 426

volume

  • 4

issue

  • 5

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