Pluripotent stem cells (PSCs) are thought to undergo a metabolic switch when they differentiate, transitioning from a primarily glycolytic state to one that is driven by mitochondrial oxidative phosphorylation. However, this observation is based mostly on studies of endoderm and mesoderm differentiation; by contrast, the metabolic requirements of ectoderm differentiation are less well-defined. To address this, Jarmon Lees and co-workers examine the metabolic changes that occur during the differentiation of human PSCs into neural precursor cells (NPCs). They demonstrate that mitochondrial DNA copy number, mitochondrial mass and mitochondrial activity initially peak at the onset of differentiation but then decline over the course of NPC induction. In line with this, they report that the consumption of pyruvate, lactate and glucose increases within the first 24 hours of differentiation but then declines. By contrast, the glycolytic rate (as determined by the relative concentrations of glucose and lactate) gradually increases during NPC induction, indicating that nascent neural differentiation involves heightened glycolytic activity. Together, these findings reveal that PSCs undergo an early and transient burst in metabolic activity as they differentiate, presumably as they exit pluripotency, and suggest that the established metabolic model of PSC differentiation is not applicable to ectoderm development.
