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Metabolic oxidation regulates embryonic stem cell differentiation

Academic Article
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Overview

related to degree

  • Hsu, Julie Clark, Ph.D. in Chemical Biology, Scripps Research 2004 - 2009

authors

  • Yanes, O.
  • Hsu, Julie Clark
  • Wong, D. M.
  • Patti, G. J.
  • Sanchez-Ruiz, A.
  • Benton, H. P.
  • Trauger, S. A.
  • Desponts, C.
  • Ding, Sheng
  • Siuzdak, Gary

publication date

  • June 2010

journal

  • Nature Chemical Biology  Journal

abstract

  • Metabolites offer an important unexplored complementary approach to understanding the pluripotency of stem cells. Using MS-based metabolomics, we show that embryonic stem cells are characterized by abundant metabolites with highly unsaturated structures whose levels decrease upon differentiation. By monitoring the reduced and oxidized glutathione ratio as well as ascorbic acid levels, we demonstrate that the stem cell redox status is regulated during differentiation. On the basis of the oxidative biochemistry of the unsaturated metabolites, we experimentally manipulated specific pathways in embryonic stem cells while monitoring the effects on differentiation. Inhibition of the eicosanoid signaling pathway promoted pluripotency and maintained levels of unsaturated fatty acids. In contrast, downstream oxidized metabolites (for example, neuroprotectin D1) and substrates of pro-oxidative reactions (for example, acyl-carnitines), promoted neuronal and cardiac differentiation. We postulate that the highly unsaturated metabolome sustained by stem cells allows them to differentiate in response to in vivo oxidative processes such as inflammation.

subject areas

  • Amino Acids
  • Carboxylic Acids
  • Carnitine
  • Cell Differentiation
  • Eicosanoids
  • Embryonic Stem Cells
  • Gene Expression Regulation
  • Glutathione
  • Humans
  • Oxidation-Reduction
  • Phenotype
  • Proteome
  • Software
  • Stem Cells
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Identity

PubMed Central ID

  • PMC2873061

International Standard Serial Number (ISSN)

  • 1552-4450

Digital Object Identifier (DOI)

  • 10.1038/nchembio.364

PubMed ID

  • 20436487
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Additional Document Info

start page

  • 411

end page

  • 417

volume

  • 6

issue

  • 6

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