Dependence of Mouse Embryonic Stem Cells on Threonine Catabolism

Jian Wang, Peter Alexander, Leeju Wu, Robert E Hammer, Ondine Cleaver, Steven L McKnight

Research output: Contribution to journalArticle

220 Scopus citations

Abstract

Measurements of the abundance of common metabolites in cultured embryonic stem (ES) cells revealed an unusual state with respect to one-carbon metabolism. These findings led to the discovery of copious expression of the gene encoding threonine dehydrogenase (TDH) in ES cells. TDH-mediated catabolism of threonine takes place in mitochondria to generate glycine and acetylcoenzyme A (CoA), with glycine facilitating one-carbon metabolism via the glycine cleavage system and acetyl-CoA feeding the tricarboxylic acid cycle. Culture media individually deprived of each of the 20 amino acids were applied to ES cells, leading to the discovery that ES cells are critically dependent on one amino acid-threonine. These observations show that ES cells exist in a highflux backbone metabolic state comparable to that of rapidly growing bacterial cells.

Original languageEnglish (US)
Pages (from-to)435-439
Number of pages5
JournalScience
Volume325
Issue number5939
DOIs
StatePublished - Jul 24 2009

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