A Metabolic Roadmap for Somatic Stem Cell Fate

While metabolism was initially thought to play a passive role in cell biology by generating ATP to meet bioenergetic demands, recent studies have identified critical roles for metabolism in the generation of new biomass and provision of obligate substrates for the epigenetic modification of histones and DNA. This review details how metabolites generated through glycolysis and the tricarboxylic acid cycle are utilized by somatic stem cells to support cell proliferation and lineage commitment. Importantly, we also discuss the evolving hypothesis that histones can act as an energy reservoir during times of energy stress. Finally, we discuss how cells integrate both extrinsic metabolic cues and intrinsic metabolic machinery to regulate cell fate. In this review, the authors examine the role of metabolism in regulating cell fate decisions, with a focus on metabolites supporting proliferation and lineage specification. They highlight the reciprocal regulation between metabolism and epigenetics, exploring ways in which cells sense nutrient availability.