Concise Review: Energy Metabolites: Key Mediators of the Epigenetic State of Pluripotency

Abstract

Recent studies suggest that the metabolic network is an important part of the molecular circuitry that underlies pluripotency. Of the metabolic pathways that were implicated in the pluripotency balance, "energy" metabolism is particularly notable. Its mechanism of action on pluripotency-regulating genes has been partially elucidated when three metabolites, namely acetate, S-adenosylmethionine, and O-linked β-N-acetylglucosamine were recently shown to link cytosolic signals to pluripotent gene expression. The cytosolic levels of these metabolites are the result of environmental perturbations, making them sensitive messengers, which are assumed to diffuse through the nuclear pores, being small molecules. Recent work also suggests that the modulation of the levels of these metabolites in pluripotent cells controls the balance between pluripotency and early commitment via epigenetic modifications. Here, we review recent studies that link metabolism and pluripotency via epigenetic modifications that occur through these three metabolites. Stem Cells 2015;33:2374-2380