Transition from glycolysis to oxidative phosphorylation during HSC differentiation. Normal HSCs are known to be located in a low-oxygen niche environment and rely mostly on glycolysis. HSC differentiation is associated with elevation of ROS, mammalian target of rapamycin (mTOR) activation, enhanced mitochondrial biogenesis, and a switch to oxidative phosphorylation (OXPHOS) and increased oxygen consumption. ADP, adenosine 5′-diphosphate; ATP, adenosine triphosphate; Diff, differentiated cell; ETC, electron transport chain; TCA, tricarboxylic acid.