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Extracellular vesicles from neural stem cells transfer IFN-γ via Ifngr1 to activate Stat1 signaling in target cells.
Cossetti, Chiara; Iraci, Nunzio; Mercer, Tim R; Leonardi, Tommaso; Alpi, Emanuele; Drago, Denise; Alfaro-Cervello, Clara; Saini, Harpreet K; Davis, Matthew P; Schaeffer, Julia; Vega, Beatriz; Stefanini, Matilde; Zhao, CongJian; Muller, Werner; Garcia-Verdugo, Jose Manuel; Mathivanan, Suresh; Bachi, Angela; Enright, Anton J; Mattick, John S; Pluchino, Stefano.
Afiliação
  • Cossetti C; John van Geest Centre for Brain Repair, Department of Clinical Neurosciences, and NIHR Biomedical Research Centre, University of Cambridge, CB2 0PY Cambridge, UK; Wellcome Trust-Medical Research Council Stem Cell Institute, Cambridge, UK.
  • Iraci N; John van Geest Centre for Brain Repair, Department of Clinical Neurosciences, and NIHR Biomedical Research Centre, University of Cambridge, CB2 0PY Cambridge, UK; Wellcome Trust-Medical Research Council Stem Cell Institute, Cambridge, UK.
  • Mercer TR; Institute for Molecular Bioscience, University of Queensland, St Lucia QLD 4072, Australia.
  • Leonardi T; John van Geest Centre for Brain Repair, Department of Clinical Neurosciences, and NIHR Biomedical Research Centre, University of Cambridge, CB2 0PY Cambridge, UK; Wellcome Trust-Medical Research Council Stem Cell Institute, Cambridge, UK; The EMBL-European Bioinformatics Institute, Wellcome Trust Ge
  • Alpi E; Biomolecular Mass Spectrometry Unit, Division of Genetics and Cell Biology, San Raffaele Scientific Institute, 20132 Milano, Italy.
  • Drago D; Biomolecular Mass Spectrometry Unit, Division of Genetics and Cell Biology, San Raffaele Scientific Institute, 20132 Milano, Italy.
  • Alfaro-Cervello C; John van Geest Centre for Brain Repair, Department of Clinical Neurosciences, and NIHR Biomedical Research Centre, University of Cambridge, CB2 0PY Cambridge, UK; Wellcome Trust-Medical Research Council Stem Cell Institute, Cambridge, UK.
  • Saini HK; The EMBL-European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SD, UK.
  • Davis MP; The EMBL-European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SD, UK.
  • Schaeffer J; John van Geest Centre for Brain Repair, Department of Clinical Neurosciences, and NIHR Biomedical Research Centre, University of Cambridge, CB2 0PY Cambridge, UK; Wellcome Trust-Medical Research Council Stem Cell Institute, Cambridge, UK.
  • Vega B; John van Geest Centre for Brain Repair, Department of Clinical Neurosciences, and NIHR Biomedical Research Centre, University of Cambridge, CB2 0PY Cambridge, UK; Wellcome Trust-Medical Research Council Stem Cell Institute, Cambridge, UK.
  • Stefanini M; John van Geest Centre for Brain Repair, Department of Clinical Neurosciences, and NIHR Biomedical Research Centre, University of Cambridge, CB2 0PY Cambridge, UK; Wellcome Trust-Medical Research Council Stem Cell Institute, Cambridge, UK.
  • Zhao C; Southwest Hospital, Southwest Eye Hospital, Third Military Medical University, Chongqing 400038, China.
  • Muller W; Faculty of Life Sciences, University of Manchester, Manchester M13 9PT, UK.
  • Garcia-Verdugo JM; Departamento de Neurobiología Comparada, Instituto Cavanilles, Universidad de Valencia, 46980 Valencia, Spain.
  • Mathivanan S; Department of Biochemistry, La Trobe Institute for Molecular Sciences, La Trobe University, Bundoora, Victoria 3086, Australia.
  • Bachi A; Biomolecular Mass Spectrometry Unit, Division of Genetics and Cell Biology, San Raffaele Scientific Institute, 20132 Milano, Italy.
  • Enright AJ; The EMBL-European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SD, UK.
  • Mattick JS; The Garvan Institute, Darlinghurst, NSW 2010, Australia.
  • Pluchino S; John van Geest Centre for Brain Repair, Department of Clinical Neurosciences, and NIHR Biomedical Research Centre, University of Cambridge, CB2 0PY Cambridge, UK; Wellcome Trust-Medical Research Council Stem Cell Institute, Cambridge, UK. Electronic address: spp24@cam.ac.uk.
Mol Cell ; 56(2): 193-204, 2014 Oct 23.
Article em En | MEDLINE | ID: mdl-25242146
ABSTRACT
The idea that stem cell therapies work only via cell replacement is challenged by the observation of consistent intercellular molecule exchange between the graft and the host. Here we defined a mechanism of cellular signaling by which neural stem/precursor cells (NPCs) communicate with the microenvironment via extracellular vesicles (EVs), and we elucidated its molecular signature and function. We observed cytokine-regulated pathways that sort proteins and mRNAs into EVs. We described induction of interferon gamma (IFN-γ) pathway in NPCs exposed to proinflammatory cytokines that is mirrored in EVs. We showed that IFN-γ bound to EVs through Ifngr1 activates Stat1 in target cells. Finally, we demonstrated that endogenous Stat1 and Ifngr1 in target cells are indispensable to sustain the activation of Stat1 signaling by EV-associated IFN-γ/Ifngr1 complexes. Our study identifies a mechanism of cellular signaling regulated by EV-associated IFN-γ/Ifngr1 complexes, which grafted stem cells may use to communicate with the host immune system.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Interferon gama / Receptores de Interferon / Vesículas Transportadoras / Células-Tronco Neurais Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Ano de publicação: 2014 Tipo de documento: Article
Texto completo
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XML
PubMed Links
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Interferon gama / Receptores de Interferon / Vesículas Transportadoras / Células-Tronco Neurais Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Ano de publicação: 2014 Tipo de documento: Article