Figure 1.

Stem cell metabolism is dynamically modulated to control stemness, proliferation, and cell commitment. Quiescent stem cells are mostly glycolytic due to HIF-1α activity in the hypoxic niche with low generation of ROS to maintain stemness. Outside the hypoxic niche, the oxygen levels begin to rise increasing the oxidative phosphorylation (OxPhos) and reactive oxygen species (ROS) levels, which stimulate the cells to proliferate and differentiate. During proliferation, stem cells mainly rely on glycolysis while still maintaining low OxPhos levels to fuel the cells with biosynthetic intermediates important for cell growth. Stem cell differentiation to cardiomyocytes, however, depends on a metabolic shift from glycolysis to OxPhos in a ROS-dependent manner.