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Metabolic trajectories in developing human neocortical neurons.

Gianmarco Ferri1, Francesco Finamore1, Francesco Greco1,2

  • 1Fondazione Pisana per la Scienza ONLUS, San Giuliano Terme, Italy 56017, Italy.

Proceedings of the National Academy of Sciences of the United States of America
|March 31, 2026
PubMed
Summary

Human neural stem cells reveal how metabolism shifts during neuron development. This study maps metabolic changes during corticogenesis, aiding research into neurometabolic disorders.

Keywords:
metabolismneocortical developmentneuronal differentiation

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Area of Science:

  • Neuroscience
  • Developmental Biology
  • Metabolic Research

Background:

  • The metabolic shift from glycolysis to oxidative phosphorylation is crucial for neural differentiation.
  • The precise timing of this metabolic rewiring during human corticogenesis is not well understood.

Purpose of the Study:

  • To investigate the spatiotemporal dynamics of metabolic pathways during human cortical neuron development.
  • To map metabolic adaptations from neuroepithelial stem cells to functional neurons.

Main Methods:

  • Utilized a neocortex-derived human neuroepithelial stem cell platform for a 4-month longitudinal study.
  • Employed quantitative proteomics, NAD(P)H fluorescence lifetime imaging, and metabolomics.
  • Validated findings in human neocortical specimens.

Main Results:

  • Detailed the metabolic pathway changes throughout neuronal differentiation and the acquisition of electrophysiological competence.
  • Identified key metabolic adaptations driving cortical neuron maturation.
  • Established a temporal map of neocortical metabolism during development.

Conclusions:

  • Provides a comprehensive spatiotemporal map of neocortical metabolism during human development.
  • Offers a framework for studying human neurometabolic disorders.
  • Highlights the critical role of metabolic rewiring in neuronal maturation.