Transition from glycolysis to OXPHOS during HSC differentiation. HSCs are known to reside in a hypoxic BM niche and to rely on anaerobic glycolysis. Hypoxic conditions activate HIF-1α, which promotes the activation of PDK. PDK in turns prevents pyruvate entry to the TCA cycle by inhibiting PDH. HSC differentiation is associated with elevation of ROS owing to a metabolic switch toward OXPHOS and increased oxygen consumption. LT-HSC, long-term hematopoietic stem cell.