Development of Cellular Energy Metabolism During Differentiation of Human iPSCs Into Cortical Neurons

We performed label-free quantitative proteomic profiling to characterize metabolic remodeling during early differentiation of human iPSCs into excitatory cortical neurons induced by NGN2 overexpression. Proteomic analysis was conducted at three time-points (iPSCs, day 7, and day 14 post-induction), focusing on neuronal, mitochondrial, and biosynthetic pathways. Our findings identify the first week of neuronal differentiation as a critical period characterized by coordinated proteomic and metabolic reprogramming, including the suppression of pluripotency markers, acquisition of neuronal identity, and reduced proliferation. Mitochondrial biogenesis is initiated during this phase, accompanied by the upregulation of oxidative phosphorylation and fatty acid oxidation. These data establish a proteomic baseline for cortical neuron differentiation and provide a reference platform for the interpretation of metabolic alterations in patient-derived models.