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dc.contributor.authorSilva, Maria Elenaen
dc.contributor.authorLange, Simonaen
dc.contributor.authorHinrichsen, Bryanen
dc.contributor.authorPhilp, Amber Ren
dc.contributor.authorReyes, Carolina Ren
dc.contributor.authorHalabi, Diegoen
dc.contributor.authorMansilla, Josselyne Ben
dc.contributor.authorRotheneichner, Peteren
dc.contributor.authorGuzman de la Fuente, Alerieen
dc.contributor.authorCouillard-Despres, Sebastienen
dc.contributor.authorBátiz, Luis Fen
dc.contributor.authorFranklin, Robinen
dc.contributor.authorAigner, Ludwigen
dc.contributor.authorRivera, Francisco Jen
dc.date.accessioned2019-04-01T08:57:52Z
dc.date.available2019-04-01T08:57:52Z
dc.date.issued2019-01en
dc.identifier.issn1662-5102
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/291008
dc.description.abstractMultiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system (CNS). Upon demyelination, oligodendrocyte progenitor cells (OPCs) are activated and they proliferate, migrate and differentiate into myelin-producing oligodendrocytes. Besides OPCs, neural stem cells (NSCs) may respond to demyelination and generate oligodendrocytes. We have recently shown that CNS-resident pericytes (PCs) respond to demyelination, proliferate and secrete Laminin alpha2 (Lama2) that, in turn, enhances OPC differentiation. Here, we aimed to evaluate whether PCs influence the fate choice of NSCs in vitro, towards the production of new myelin-producing cells. Indeed, upon exposure to conditioned medium derived from PCs (PC-CM), the majority of NSCs gave rise to GalC- and MBP-expressing oligodendrocytes at the expense of the generation of GFAP-positive astrocytes. Consistent with these findings, PC-CM induces an increase in the expression of the oligodendrocyte fate determinant Olig2, while the expression level of the astrocyte determinant ID2 is decreased. Finally, pre-incubation of PC-CM with an anti-Lama2 antibody prevented the generation of oligodendrocytes. Our findings indicate that PCs-derived Lama2 instructs NSCs to an oligodendrocyte fate choice favouring the generation of myelin-producing cells at the expense of astrocytes in vitro. Further studies aiming to reveal the role of PCs during remyelination may pave the way for the development of new therapies for the treatment of MS.
dc.description.sponsorshipThe authors would like to thank the following funding agencies for their support: Paracelsus Medical University PMU-FFF Long-Term Fellowship L-12/01/001-RIV (to and Stand-Alone Grant E-12/15/077-RIT (both to F.J.R.); Chilean FONDECYT Program CONICYT Grant Nº 1161787 (F.J.R.), Grant Nº 1141015 (L.F.B); Chilean PCI Program CONICYT Grant Nº REDES170233, Grant Nº REDES180139 and Grant Nº REDI170037 (all to F.J.R); Chilean FONDEF-IDeA Program Grant Nº ID17AM0043 (M.E.S. and F.J.R.); the Bavarian State Ministry of Sciences, Research and the Arts (ForNeuroCell grant) (L.A.); the Germany Federal Ministry of Education and Research (BMBF grants #0312134, #01GG0706 and #01GN0505); European Union's Seventh Framework Programme (FP7/2007-2013) under grant agreements n° HEALTH-F2-2011-278850 (INMiND) and HEALTH-F2-2011-279288 (IDEA). The work in the Franklin laboratory was supported by a programme grant from the UK Multiple Sclerosis Society and Adelson Medical Research Foundation and a core support grant from the Wellcome Trust and MRC to the Wellcome Trust-MRC Cambridge Stem Cell Institute. In addition, the present work was supported by the state of Salzburg (to L.A.).
dc.format.mediumElectronic-eCollectionen
dc.languageengen
dc.publisherFrontiers Media
dc.rightsAttribution 4.0 International*
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/*
dc.titlePericytes Favor Oligodendrocyte Fate Choice in Adult Neural Stem Cells.en
dc.typeArticle
prism.publicationDate2019en
prism.publicationNameFrontiers in cellular neuroscienceen
prism.startingPage85
prism.volume13en
dc.identifier.doi10.17863/CAM.38187
dcterms.dateAccepted2019-02-20en
rioxxterms.versionofrecord10.3389/fncel.2019.00085en
rioxxterms.versionVoR*
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserveden
rioxxterms.licenseref.startdate2019-01en
dc.contributor.orcidSilva, Maria Elena [0000-0001-6236-7180]
dc.contributor.orcidHalabi, Diego [0000-0002-1474-8066]
dc.contributor.orcidBátiz, Luis F [0000-0002-3043-8797]
dc.contributor.orcidFranklin, Robin [0000-0001-6522-2104]
dc.contributor.orcidAigner, Ludwig [0000-0002-1653-8046]
dc.contributor.orcidRivera, Francisco J [0000-0001-7895-6318]
dc.identifier.eissn1662-5102
rioxxterms.typeJournal Article/Reviewen
pubs.funder-project-idMRC (MC_PC_12009)
cam.orpheus.successThu Jan 30 10:49:12 GMT 2020 - The item has an open VoR version.*
rioxxterms.freetoread.startdate2100-01-01


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Attribution 4.0 International
Except where otherwise noted, this item's licence is described as Attribution 4.0 International