Dependence of Mouse Embryonic Stem Cells on Threonine Catabolism
Jian Wang,1
Peter Alexander,1
Leeju Wu,1
Robert Hammer,1
Ondine Cleaver,2
Steven L. McKnight1,*
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 acetyl–coenzyme
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 high-flux backbone
metabolic state comparable to that of rapidly growing bacterial
cells.
2 Department of Molecular Biology, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390–9152, USA.
* To whom correspondence should be addressed. E-mail: steven.mcknight{at}utsouthwestern.edu
