Research led by Dr. Steven McKnight of UT Southwestern Medical Center has demonstrated that the activation of a particular gene encoding threonine dehydrogenase (TDH) may be a key component of why mouse embryonic stem cells are easily grown in a laboratory while other mammalian ES cells are difficult, if not impossible, to maintain.
Here’s the 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 acetyl-CoA, with glycine facilitating one-carbon metabolism via the glycine cleavage system and acetyl-CoA feeding the tricarboxcylic acid (TCA) 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 upon but one amino acid—threonine. These observations show that ES cells exist in a unique, high-flux backbone metabolic state comparable to that of rapidly growing bacterial cells.
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