SAM, Histones, and Stem Cells Mouse embryonic stem cells require threonine for growth and express large amounts of the enzyme that catalyzes the first step in threonine metabolism. To find out what is so important about threonine in these cells, Shyh-Change et al. (p. 222 , published online 1 November; see the Perspective by Sassone-Corsi ) monitored changes in metabolism by mass spectrometry in induced pluripotent stem cells. Threonine was required to maintain cellular concentrations of S-adenosylmethionine (SAM), a substrate used for protein methylation. Restriction of threonine inhibited methylation of histones, which is characteristic of chromatin in embryonic stem cells. Thus, altered metabolism of threonine and methionine in stem cells may be linked to epigenetic changes that influence genetic reprogramming and decisions of stem cells to proliferate or differentiate.