Metabolic trajectories in developing human neocortical neurons
Abstract
The shift from glycolysis to oxidative phosphorylation is a key step in neural differentiation. Yet, the timing of metabolic rewiring in the development from progenitors to neurons remains elusive, especially in human corticogenesis. To bridge this gap, here we adopted a unique cell platform based on neocortex-derived human neuroepithelial stem cells, modeling their physiological transition into functional neurons in a 4-mo longitudinal study and until the acquisition of electrophysiological competence. Using quantitative proteomics, combined with NAD(P)H fluorescence lifetime imaging and metabolomics, we investigated the entire differentiation process and describe how metabolic pathways drive cortical neuron maturation. The prevalent metabolic adaptations were then confirmed in a human neocortical specimen. This study provides a spatiotemporal map of neocortical metabolism during development and offers a framework to investigate human neurometabolic disorders.
Article Details
Journal Info
Proceedings of the National Academy of Sciences
National Academy of Sciences
Authors (16)
Gianmarco Ferri
Fondazione Pisana per la Scienza ONLUS
Francesco Finamore
Fondazione Pisana per la Scienza ONLUS
Francesco Greco
Fondazione Pisana per la Scienza ONLUS
Alessio Zanelli
Department of Biology Unit of Cell, Molecular and Developmental Biology, University of Pisa
Fabrizia Carli
Institute of Clinical Physiology, National Research Council
Alessandro Passera
Fondazione Pisana per la Scienza ONLUS
Elisa Degl’Innocenti
Fondazione Pisana per la Scienza ONLUS
Francesco Olimpico
Fondazione Pisana per la Scienza ONLUS
Riccardo Ducoli
Institute of Clinical Physiology, National Research Council
Agnese Sgalippa
Fondazione Pisana per la Scienza ONLUS
Gian Carlo Demontis
Department of Pharmacy, University of Pisa
Amalia Gastaldelli
Institute of Clinical Physiology, National Research Council
Francesco Cardarelli
National Enterprise for nanoScience and nanoTechnology Laboratory, Scuola Normale Superiore
Marco Onorati
Department of Biology, University of Pisa, via Luca Ghini 13, Pisa 56126, Italy
Liam A. McDonnell
Fondazione Pisana per la Scienza ONLUS
Maria Teresa Dell’Anno
Fondazione Pisana per la Scienza ONLUS