Fig. 1.

Energy sources in stem and differentiated cells. Many stem cell niches exhibit low oxygen concentrations. Stem cells appear to generate ATP mainly through glycolysis, which is independent of oxygen. Under low oxygen (<9% O₂), the hypoxia-inducible factor 1α (HIF1α) is stabilized and binds to its partner HIF1β. The HIF1 heterodimer binds to hypoxia response elements to control the expression of genes involved in glucose metabolism and transport, the cell cycle and cell death. HIF1 activity appears to have an active role in the regulation of stem cell metabolism, as it can induce stem cells to shift towards a predominantly anaerobic glycolytic metabolism. Conversely, differentiated cells generate ATP largely through oxidative phosphorylation, which requires oxygen. ETC, electron transport chain; TCA, tricarboxylic acid.