Modulating the serine metabolism in human differentiated astrocytes: an integrated multi omics approach
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Le résumé fourni par la source
Introduction: Astrocytes are the major source of L-serine (L-Ser) in the brain: the glycolytic intermediate D-3-phosphoglycerate is converted into L-Ser through the phosphorylated pathway (PP) made up of three enzymes, phosphoglycerate dehydrogenase (PHGDH), phosphoserine aminotransferase (PSAT) and phosphoserine phosphatase (PSP), recently proposed to generate a metabolic assembly named serinosome. In the central nervous system, L-Ser is used for a number of functions, including the synthesis of glycine (Gly) and D-serine (D-Ser), the two key NMDAR co-agonists. Methods: Here, we used iPSC-derived human astrocytes as a cellular model to evaluate the impact on cell metabolism of the overexpression of each of the three enzymes of the PP as GFP-tagged proteins. Results: The subcellular cytosolic localization of PP enzymes remains unchanged compared to endogenous proteins, while the complex formation is increased in all cases. Notably, among the factors involved, the overexpression of PHGDH appears to play a pivotal role in promoting the serinosome assembly and/or stabilization, highlighting the critical importance of this multi-domain protein. Particularly, the overexpression of each enzyme of the PP alters the cellular metabolism in a specific way. The L-Ser and Gly levels increase more in PHGDH overexpressing cells, in agreement with the known kinetics of the PP. A consistent increase in the TCA cycle, as well as in mitochondrial activities, serine-glycine-one carbon pathway, asparagine, arginine, purine and pyrimidines metabolism is also observed. Discussion: Peculiar alterations are observed when each enzyme of the PP is overexpressed, strongly supporting the use of human iPSC-derived astrocytes overexpressing the PP pathway enzymes as a valuable cellular model for understanding how Ser glial metabolism occurs in a non-tumor system under both physiological and pathological conditions.
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Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.
- Titre Crossref
- Modulating the serine metabolism in human differentiated astrocytes: an integrated multi omics approach
- Date Crossref
- 21/07/2025
- Éditeur
- Frontiers Media SA
- 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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University of Milano-Bicocca Department of Biotechnology and Biosciences pays non établi dans la noticeUniversité ou école supérieure
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University of Milan pays non établi dans la noticeUniversité ou école supérieure
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University of Insubria The Protein Factory 2.0 Laboratory pays non établi dans la noticeUniversité ou école supérieure
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Construction Technologies Institute pays non établi dans la noticeStructure de recherche
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Institute of Biomedical Technologies pays non établi dans la noticeStructure de recherche
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National Research Council pays non établi dans la noticeOrganisation à but non lucratif
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Institute for Biomedical Technologies pays non établi dans la noticeStructure de recherche
Department of Biotechnology and Biosciences — University of Milano-Bicocca, University of Milan et The Protein Factory 2.0 Laboratory — University of Insubria, avec 4 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.