title: Demyelination causes adult CNS progenitors to revert to an immature state and express immune cues that support their migration.
abstract: The declining efficiency of myelin regeneration in individuals with multiple sclerosis has stimulated a search for ways by which it might be therapeutically enhanced. Here we have used gene expression profiling on purified murine oligodendrocyte progenitor cells (OPCs), the remyelinating cells of the adult CNS, to obtain a comprehensive picture of how they become activated after demyelination and how this enables them to contribute to remyelination. We find that adult OPCs have a transcriptome more similar to that of oligodendrocytes than to neonatal OPCs, but revert to a neonatal-like transcriptome when activated. Part of the activation response involves increased expression of two genes of the innate immune system, IL1β and CCL2, which enhance the mobilization of OPCs. Our results add a new dimension to the role of the innate immune system in CNS regeneration, revealing how OPCs themselves contribute to the postinjury inflammatory milieu by producing cytokines that directly enhance their repopulation of areas of demyelination and hence their ability to contribute to remyelination.
authors.affiliation: Université Pierre et Marie Curie-Paris 6, Centre de Recherche de l'Institut du Cerveau et de la Moelle Épinière, 75013 Paris, France, Institut National de la Santé et de la Recherche Médicale, U 1127, 75013 Paris, France, CNRS, Unite Mixte de Recherche 7225, 75013 Paris, France.
authors.forename: Sarah
authors.initials: S
authors.lastname: Moyon
authors.affiliation: Université Pierre et Marie Curie-Paris 6, Centre de Recherche de l'Institut du Cerveau et de la Moelle Épinière, 75013 Paris, France, Institut National de la Santé et de la Recherche Médicale, U 1127, 75013 Paris, France, CNRS, Unite Mixte de Recherche 7225, 75013 Paris, France.
authors.forename: Anne Laure
authors.initials: AL
authors.lastname: Dubessy
authors.affiliation: Université Pierre et Marie Curie-Paris 6, Centre de Recherche de l'Institut du Cerveau et de la Moelle Épinière, 75013 Paris, France, Institut National de la Santé et de la Recherche Médicale, U 1127, 75013 Paris, France, CNRS, Unite Mixte de Recherche 7225, 75013 Paris, France.
authors.forename: Marie Stephane
authors.initials: MS
authors.lastname: Aigrot
authors.affiliation: Anne McLaren Laboratory for Regenerative Medicine, University of Cambridge, Forvie Site, Cambridge CB2 0SZ, United Kingdom, and.
authors.forename: Matthew
authors.initials: M
authors.lastname: Trotter
authors.affiliation: Department of Clinical Neuroscience, Wellcome Trust-Medical Research Council Cambridge Stem Cell Institute, University of Cambridge, Cambridge CB3 0ES, United Kingdom.
authors.forename: Jeffrey K
authors.initials: JK
authors.lastname: Huang
authors.affiliation: Université Pierre et Marie Curie-Paris 6, Centre de Recherche de l'Institut du Cerveau et de la Moelle Épinière, 75013 Paris, France, Institut National de la Santé et de la Recherche Médicale, U 1127, 75013 Paris, France, CNRS, Unite Mixte de Recherche 7225, 75013 Paris, France.
authors.forename: Luce
authors.initials: L
authors.lastname: Dauphinot
authors.affiliation: Université Pierre et Marie Curie-Paris 6, Centre de Recherche de l'Institut du Cerveau et de la Moelle Épinière, 75013 Paris, France, Institut National de la Santé et de la Recherche Médicale, U 1127, 75013 Paris, France, CNRS, Unite Mixte de Recherche 7225, 75013 Paris, France.
authors.forename: Marie Claude
authors.initials: MC
authors.lastname: Potier
authors.affiliation: Institut Hospitalo Universitaire-A-Institut du Cerveau et de la Moelle Épinière, 75013 Paris, France.
authors.forename: Christophe
authors.initials: C
authors.lastname: Kerninon
authors.affiliation: Institut de la Vision, UMRS 968, UMR 7210 CNRS, Université Pierre et Marie Curie-Paris 6, 75012 Paris, France.
authors.forename: Stephane
authors.initials: S
authors.lastname: Melik Parsadaniantz
authors.affiliation: Department of Clinical Neuroscience, Wellcome Trust-Medical Research Council Cambridge Stem Cell Institute, University of Cambridge, Cambridge CB3 0ES, United Kingdom, catherine.lubetzki@psl.aphp.fr rjf1000@cam.ac.uk.
authors.forename: Robin J M
authors.initials: RJ
authors.lastname: Franklin
authors.affiliation: Université Pierre et Marie Curie-Paris 6, Centre de Recherche de l'Institut du Cerveau et de la Moelle Épinière, 75013 Paris, France, Institut National de la Santé et de la Recherche Médicale, U 1127, 75013 Paris, France, CNRS, Unite Mixte de Recherche 7225, 75013 Paris, France, Groupe Hospitalier Pitié-Salpêtrière, 75013 Paris, France, catherine.lubetzki@psl.aphp.fr rjf1000@cam.ac.uk.
authors.forename: Catherine
authors.initials: C
authors.lastname: Lubetzki
mesh_terms: D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D002465:Cell Movement / Q000276:immunology*; D003711:Demyelinating Diseases / Q000276:immunology* / Q000473:pathology; D005260:Female; D007113:Immunity, Innate / Q000276:immunology*; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D058953:Neural Stem Cells / Q000276:immunology*; D055495:Neurogenesis / Q000276:immunology*; D051381:Rats; D013552:Swine
keywords: Oligodendrocyte progenitor cells; cytokines; migration; multiple sclerosis; remyelination