Metabolism in physiological cell proliferation and differentiation

•Metabolic changes are involved in cell proliferation and differentiation during embryogenesis and in stem cells.•Metabolism is regulated by the signaling pathways that control cell proliferation and differentiation.•Metabolites can regulate cell signaling.

Stem and progenitor cells proliferate and give rise to other types of cells through differentiation. Deregulation of this process can lead to many diseases including cancer. Recent evidence suggests that an extensive metabolic reconfiguration of cancer cells allows them to sustain pathological growth by providing anabolic intermediates for biosynthesis. This raises the question of the physiological role of metabolic pathways during normal cell growth and differentiation. Metabolism changes with differentiation, and metabolic pathways may be controlled by the same signals that control cell proliferation and differentiation. However, metabolism could also reciprocally influence these signals. The role of metabolic regulation may extend beyond the provision of intermediates for the biosynthetic needs of proliferation, to affect cell differentiation. Here we bring together a large number of recent studies that support this suggestion and illustrate some of the mechanisms by which metabolism is linked to cell proliferation and differentiation.