@article {269976,
	title = {Metabolic oxidation regulates embryonic stem cell differentiation},
	journal = {Nat Chem BiolNat Chem BiolNat Chem Biol},
	volume = {6},
	year = {2010},
	note = {Yanes, OscarClark, JulieWong, Diana MPatti, Gary JSanchez-Ruiz, AntonioBenton, H PaulTrauger, Sunia ADesponts, CarolineDing, ShengSiuzdak, GaryR24 EY017540/EY/NEI NIH HHS/R24 EY017540-03/EY/NEI NIH HHS/R24 EY017540-05/EY/NEI NIH HHS/Nat Chem Biol. 2010 Jun;6(6):411-7. doi: 10.1038/nchembio.364. Epub 2010 May 2.},
	month = {Jun},
	pages = {411-7},
	type = {Research Support, N.I.H., ExtramuralResearch Support, Non-U.S. Gov{\textquoteright}tResearch Support, U.S. Gov{\textquoteright}t, Non-P.H.S.},
	edition = {2010/05/04},
	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.},
	keywords = {Amino Acids/metabolism, Carboxylic Acids/metabolism, Carnitine/metabolism, Cell Differentiation, Eicosanoids/metabolism, Embryonic Stem Cells/*cytology/*metabolism, Gene Expression Regulation, Glutathione/metabolism, Humans, Oxidation-Reduction, Phenotype, Proteome/metabolism, Software, Stem Cells/cytology/metabolism},
	isbn = {1552-4469 (Electronic)1552-4450 (Linking)},
	author = {Yanes, O. and Clark, J. and Wong, D. M. and Patti, G. J. and Sanchez-Ruiz, A. and Benton, H. P. and Trauger, S. A. and Desponts, C. and Ding, S. and Siuzdak, G.}
}
