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https://observatorio.fm.usp.br/handle/OPI/47253
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DC Field | Value | Language |
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dc.contributor | Sistema FMUSP-HC: Faculdade de Medicina da Universidade de São Paulo (FMUSP) e Hospital das Clínicas da FMUSP | - |
dc.contributor.author | GHIROTTO, Bruno | - |
dc.contributor.author | OLIVEIRA, Danyllo F. | - |
dc.contributor.author | CIPELLI, Marcella | - |
dc.contributor.author | BASSO, Paulo J. | - |
dc.contributor.author | LIMA, Jean | - |
dc.contributor.author | BREDA, Cristiane N. S. | - |
dc.contributor.author | RIBEIRO, Henrique C. | - |
dc.contributor.author | SILVA, Camille C. C. | - |
dc.contributor.author | SERTIE, Andrea L. | - |
dc.contributor.author | OLIVEIRA, Antonio Edson R. | - |
dc.contributor.author | I, Meire Hiyane | - |
dc.contributor.author | CALDINI, Elia G. | - |
dc.contributor.author | SUSSULINI, Alessandra | - |
dc.contributor.author | I, Helder Nakaya | - |
dc.contributor.author | KOWALTOWSKI, Alicia J. | - |
dc.contributor.author | OLIVEIRA, Enedina M. L. | - |
dc.contributor.author | ZATZ, Mayana | - |
dc.contributor.author | CAMARA, Niels O. S. | - |
dc.date.accessioned | 2022-06-20T15:32:04Z | - |
dc.date.available | 2022-06-20T15:32:04Z | - |
dc.date.issued | 2022 | - |
dc.identifier.citation | ANNALS OF NEUROLOGY, v.91, n.5, p.652-669, 2022 | - |
dc.identifier.issn | 0364-5134 | - |
dc.identifier.uri | https://observatorio.fm.usp.br/handle/OPI/47253 | - |
dc.description.abstract | Objective Astrocytes play a significant role in the pathology of multiple sclerosis (MS). Nevertheless, for ethical reasons, most studies in these cells were performed using the Experimental Autoimmune Encephalomyelitis model. As there are significant differences between human and mouse cells, we aimed here to better characterize astrocytes from patients with MS (PwMS), focusing mainly on mitochondrial function and cell metabolism. Methods We obtained and characterized induced pluripotent stem cell (iPSC)-derived astrocytes from three PwMS and three unaffected controls, and performed electron microscopy, flow cytometry, cytokine and glutamate measurements, gene expression, in situ respiration, and metabolomics. We validated our findings using a single-nuclei RNA sequencing dataset. Results We detected several differences in MS astrocytes including: (i) enrichment of genes associated with neurodegeneration, (ii) increased mitochondrial fission, (iii) increased production of superoxide and MS-related proinflammatory chemokines, (iv) impaired uptake and enhanced release of glutamate, (v) increased electron transport capacity and proton leak, in line with the increased oxidative stress, and (vi) a distinct metabolic profile, with a deficiency in amino acid catabolism and increased sphingolipid metabolism, which have already been linked to MS. Interpretation Here we describe the metabolic profile of iPSC-derived astrocytes from PwMS and validate this model as a very powerful tool to study disease mechanisms and to perform non-invasive drug targeting assays in vitro. Our findings recapitulate several disease features described in patients and provide new mechanistic insights into the metabolic rewiring of astrocytes in MS, which could be targeted in future therapeutic studies. ANN NEUROL 2022 | eng |
dc.description.sponsorship | Fundacao de Amparo a Pesquisa do Estado de Sao Paulo [2017/05264-7, 2018/23460-0, 20/06970-5, CEPID: 2013/08028-1] | - |
dc.description.sponsorship | Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior [001] | - |
dc.description.sponsorship | Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (Centro de Pesquisa, Inovacao e Difusao em Processos Redox em Biomedicina) [2013/07937-8] | - |
dc.language.iso | eng | - |
dc.publisher | WILEY | eng |
dc.relation.ispartof | Annals of Neurology | - |
dc.rights | restrictedAccess | eng |
dc.subject.other | multiple-sclerosis patients | eng |
dc.subject.other | neurodegeneration | eng |
dc.subject.other | dysfunction | eng |
dc.subject.other | immune | eng |
dc.title | MS-Driven Metabolic Alterations Are Recapitulated in iPSC-Derived Astrocytes | eng |
dc.type | article | eng |
dc.rights.holder | Copyright WILEY | eng |
dc.identifier.doi | 10.1002/ana.26336 | - |
dc.identifier.pmid | 35226368 | - |
dc.type.category | original article | eng |
dc.type.version | publishedVersion | eng |
hcfmusp.author.external | GHIROTTO, Bruno:Univ Sao Paulo, Dept Immunol, Inst Biomed Sci, Transplantat Immunobiol Lab, Sao Paulo, Brazil | - |
hcfmusp.author.external | OLIVEIRA, Danyllo F.:Univ Sao Paulo, Human Genome & Stem Cell Res Ctr, Dept Genet & Evolutionary Biol, Inst Biosci, Sao Paulo, Brazil | - |
hcfmusp.author.external | CIPELLI, Marcella:Univ Sao Paulo, Dept Immunol, Inst Biomed Sci, Transplantat Immunobiol Lab, Sao Paulo, Brazil | - |
hcfmusp.author.external | BASSO, Paulo J.:Univ Sao Paulo, Dept Immunol, Inst Biomed Sci, Transplantat Immunobiol Lab, Sao Paulo, Brazil | - |
hcfmusp.author.external | LIMA, Jean:Univ Sao Paulo, Dept Immunol, Inst Biomed Sci, Transplantat Immunobiol Lab, Sao Paulo, Brazil | - |
hcfmusp.author.external | BREDA, Cristiane N. S.:Univ Sao Paulo, Dept Immunol, Inst Biomed Sci, Transplantat Immunobiol Lab, Sao Paulo, Brazil | - |
hcfmusp.author.external | RIBEIRO, Henrique C.:Univ Estadual Campinas, Dept Analyt Chem, Lab Bioanalyt & Integrated Omics, Inst Chem, Campinas, Brazil | - |
hcfmusp.author.external | SILVA, Camille C. C.:Univ Sao Paulo, Dept Bioquim, Inst Quim, Sao Paulo, Brazil | - |
hcfmusp.author.external | SERTIE, Andrea L.:Hosp Israelita Albert Einstein, Sao Paulo, Brazil | - |
hcfmusp.author.external | OLIVEIRA, Antonio Edson R.:Univ Sao Paulo, Dept Clin & Toxicol Anal, Sch Pharmaceut Sci, Sao Paulo, Brazil; Univ Sao Paulo, Sci Platform Pasteur, Sao Paulo, SP, Brazil | - |
hcfmusp.author.external | I, Meire Hiyane:Univ Sao Paulo, Dept Immunol, Inst Biomed Sci, Transplantat Immunobiol Lab, Sao Paulo, Brazil | - |
hcfmusp.author.external | SUSSULINI, Alessandra:Univ Estadual Campinas, Dept Analyt Chem, Lab Bioanalyt & Integrated Omics, Inst Chem, Campinas, Brazil | - |
hcfmusp.author.external | I, Helder Nakaya:Hosp Israelita Albert Einstein, Sao Paulo, Brazil; Univ Sao Paulo, Dept Clin & Toxicol Anal, Sch Pharmaceut Sci, Sao Paulo, Brazil; Univ Sao Paulo, Sci Platform Pasteur, Sao Paulo, SP, Brazil | - |
hcfmusp.author.external | KOWALTOWSKI, Alicia J.:Univ Sao Paulo, Dept Bioquim, Inst Quim, Sao Paulo, Brazil | - |
hcfmusp.author.external | OLIVEIRA, Enedina M. L.:Univ Fed Sao Paulo, Escola Paulista Med, Neuroimmunol Clin, Sao Paulo, SP, Brazil | - |
hcfmusp.author.external | ZATZ, Mayana:Univ Sao Paulo, Human Genome & Stem Cell Res Ctr, Dept Genet & Evolutionary Biol, Inst Biosci, Sao Paulo, Brazil | - |
hcfmusp.author.external | CAMARA, Niels O. S.:Univ Sao Paulo, Dept Immunol, Inst Biomed Sci, Transplantat Immunobiol Lab, Sao Paulo, Brazil | - |
hcfmusp.description.beginpage | 652 | - |
hcfmusp.description.endpage | 669 | - |
hcfmusp.description.issue | 5 | - |
hcfmusp.description.volume | 91 | - |
hcfmusp.origem | WOS | - |
hcfmusp.origem.id | WOS:000769921400001 | - |
hcfmusp.origem.id | 2-s2.0-85126346338 | - |
hcfmusp.publisher.city | HOBOKEN | eng |
hcfmusp.publisher.country | USA | eng |
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dc.description.index | MEDLINE | eng |
dc.identifier.eissn | 1531-8249 | - |
hcfmusp.citation.scopus | 3 | - |
hcfmusp.scopus.lastupdate | 2024-04-12 | - |
Appears in Collections: | Artigos e Materiais de Revistas Científicas - FM/MPT Artigos e Materiais de Revistas Científicas - LIM/59 Artigos e Materiais de Revistas Científicas - ODS/03 |
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