Energy metabolism in the acquisition and maintenance of stemness

Energy metabolism is traditionally considered a reactive homeostatic system addressing stage-specific cellular energy needs. There is however growing appreciation of metabolic pathways in the active control of vital cell functions. Case in point, the stem cell lifecycle - from maintenance and acquisition of stemness to lineage commitment and specification - is increasingly recognized as a metabolism-dependent process. Indeed, metabolic reprogramming is an early contributor to the orchestrated departure from or reacquisition of stemness. Recent advances in metabolomics have helped decipher the identity and dynamics of metabolic fluxes implicated in fueling cell fate choices by regulating the epigenetic and transcriptional identity of a cell. Metabolic cues, internal and/or external to the stem cell niche, facilitate progenitor pool restitution, long-term tissue renewal or ensure adoption of cytoprotective behavior. Convergence of energy metabolism with stem cell fate regulation opens a new avenue in understanding primordial developmental biology principles with future applications in regenerative medicine practice.