Development of Cellular Energy Metabolism During Differentiation of Human iPSCs into Cortical Neurons
Rattachement africain : cz. Niveau de preuve : code pays fourni par la source.
Le résumé fourni par la source
Abstract Neuronal differentiation requires extensive metabolic remodeling to support increased energetic and biosynthetic demands. Here, we present an integrated multi-omics and functional characterization of metabolic transitions during early differentiation of human induced pluripotent stem cells (iPSCs) into excitatory cortical neurons using doxycycline-inducible overexpression of neurogenin-2 (NGN2). We analyzed parental iPSCs and induced neurons (iNs) at days 7 and 14 of differentiation, integrating gene expression profiling, label-free quantitative proteomics, high-resolution respirometry, fluorescence lifetime imaging microscopy (FLIM), and 13 C₆-glucose metabolic flux analysis. Our data reveal progressive metabolic remodeling associated with neuronal maturation, including enhanced oxidative phosphorylation, increased mitochondrial content, and respiratory capacity. Proteomic analyses showed upregulation of mitochondrial and antioxidant pathways, while FLIM indicated a progressive increase in enzyme-bound NAD(P)H, consistent with a shift toward oxidative metabolism. Notably, 13 C₆-glucose tracing revealed delayed labeling of the intracellular pool of fully labeled glucose and tricarboxylic acid cycle metabolites, together with enhanced labeling of pentose phosphate pathway intermediates and glutathione in iNs, indicating a shift toward biosynthetic and antioxidant glucose utilization during differentiation. Despite this enhancement in mitochondrial function, differentiated neurons maintained glycolytic activity, suggesting metabolic flexibility. Our results define the first week of differentiation as a critical window of metabolic specialization and establish NGN2-iPSC-derived cortical neurons as a versatile and well-characterized model system for investigating bioenergetic remodeling during early human neurodevelopment. It provides a robust foundation for mechanistic insights and high-throughput evaluation of metabolic pathways relevant to human disease.
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Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.
- Titre Crossref
- Development of Cellular Energy Metabolism During Differentiation of Human iPSCs into Cortical Neurons
- Date Crossref
- 13/11/2025
- Éditeur
- Springer Science and Business Media LLC
- Type
- journal-article
Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.
Où se fait cette recherche
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Czech Academy of Sciences pays non établi dans la noticeOrganisme public
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Charles University pays non établi dans la noticeUniversité ou école supérieure
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Second Faculty of Medicine Department of Pathophysiology pays non établi dans la noticeUniversité ou école supérieure
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Faculty of Science Department of Physiology pays non établi dans la noticeUniversité ou école supérieure
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Laboratory of Cell and Developmental Biology pays non établi dans la noticeStructure de recherche
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Laboratory of Developmental Epileptology pays non établi dans la noticeStructure de recherche
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Laboratory of Bioenergetics pays non établi dans la noticeStructure de recherche
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Laboratory of Biomathematics pays non établi dans la noticeStructure de recherche
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Laboratory of Metabolomics pays non établi dans la noticeStructure de recherche
Czech Academy of Sciences, Charles University et Department of Pathophysiology — Second Faculty of Medicine, avec 6 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.