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Mol Cell. 2014 Oct 23;56(2):193-204. doi: 10.1016/j.molcel.2014.08.020. Epub 2014 Sep 18.

Extracellular vesicles from neural stem cells transfer IFN-γ via Ifngr1 to activate Stat1 signaling in target cells.

Author information

1
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.
2
Institute for Molecular Bioscience, University of Queensland, St Lucia QLD 4072, Australia.
3
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 Genome Campus, Hinxton, Cambridge CB10 1SD, UK.
4
Biomolecular Mass Spectrometry Unit, Division of Genetics and Cell Biology, San Raffaele Scientific Institute, 20132 Milano, Italy.
5
The EMBL-European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SD, UK.
6
Southwest Hospital, Southwest Eye Hospital, Third Military Medical University, Chongqing 400038, China.
7
Faculty of Life Sciences, University of Manchester, Manchester M13 9PT, UK.
8
Departamento de Neurobiología Comparada, Instituto Cavanilles, Universidad de Valencia, 46980 Valencia, Spain.
9
Department of Biochemistry, La Trobe Institute for Molecular Sciences, La Trobe University, Bundoora, Victoria 3086, Australia.
10
The Garvan Institute, Darlinghurst, NSW 2010, Australia.
11
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.

Erratum in

  • Mol Cell. 2014 Nov 20;56(4):609.

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.

PMID:
25242146
PMCID:
PMC4578249
DOI:
10.1016/j.molcel.2014.08.020
[Indexed for MEDLINE]
Free PMC Article

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