Metabolic specialization of mouse embryonic stem cells

J. Wang, P. Alexander, S. L. McKnight

Research output: Contribution to journalArticle

22 Scopus citations

Abstract

Mouse embryonic stem (ES) cells are endowed with four unusual properties. They are exceedingly small, exhibiting an intracellular volume two to three orders of magnitude smaller than that of normal mammalian cells. Their rate of cell division, wherein cell doubling takes place in only 4-5 h, is more rapid than even the fastest growing cancer cell lines. They do not senesce. Finally, mouse ES cells retain pluripotency adequate to give rise to all cell types present in either gender of adult mice. We have investigated whether some or all of these unusual features might relate to the possibility that mouse ES cells exist in a specialized metabolic state. By evaluating the abundance of common metabolites as a function of the conversion of mouse ES cells into differentiated embryoid bodies, it was observed that the most radical changes in metabolite abundance related to cellular building blocks associated with one carbon metabolism. These observations led to the discovery that mouse ES cells use the threonine dehydrogenase (TDH) enzyme to convert threonine into acetyl-coenzyme A and glycine, thereby facilitating consumption of threonine as a metabolic fuel. Here we describe the results of a combination of nutritional and pharmacological studies, providing evidence that mouse ES cells are critically dependent on both threonine and the TDH enzyme for growth and viability.

Original languageEnglish (US)
Pages (from-to)183-193
Number of pages11
JournalCold Spring Harbor symposia on quantitative biology
Volume76
DOIs
StatePublished - Dec 1 2011

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ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Genetics

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