Multiple sclerosis iPS-derived oligodendroglia conserve their properties to functionally interact with axons and glia in vivo

Autor: Linda Ottoboni, Laura Starost, Beatriz Garcia-Diaz, Anne Baron-Van Evercooren, Sabah Mozafari, Blandine Manot-Saillet, Marion J. F. Levy, Hans R. Schöler, Timothy E. Kennedy, Gianvito Martino, Yu Kang T. Xu, Kee-Pyo Kim, Jack P. Antel, Delphine Roussel, María Cecilia Angulo, Tanja Kuhlmann
Přispěvatelé: Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), University Hospital Münster - Universitaetsklinikum Muenster [Germany] (UKM), Max Planck Institute for Molecular Biomedicine, Max-Planck-Gesellschaft, Institut de psychiatrie et neurosciences de Paris (IPNP - U1266 Inserm), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), GHU Paris Psychiatrie et Neurosciences, Montreal Neurological Institute and Hospital, McGill University = Université McGill [Montréal, Canada], IRCCS Ospedale San Raffaele [Milan, Italy], Universita Vita Salute San Raffaele = Vita-Salute San Raffaele University [Milan, Italie] (UniSR), Martinez Rico, Clara, Institut du Cerveau = Paris Brain Institute (ICM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Mozafari, S., Starost, L., Manot-Saillet, B., Garcia-Diaz, B., Xu, Y. K. T., Roussel, D., Levy, M. J. F., Ottoboni, L., Kim, K. -P., Scholer, H. R., Kennedy, T. E., Antel, J. P., Martino, G., Angulo, M. C., Kuhlmann, T., Evercooren, A. B. -V.
Jazyk: angličtina
Rok vydání: 2020
Předmět:
Zdroj: Science Advances
Science Advances, American Association for the Advancement of Science (AAAS), 2020, 6 (49), pp.eabc6983. ⟨10.1126/sciadv.abc6983⟩
Science Advances, 2020, 6 (49), pp.eabc6983. ⟨10.1126/sciadv.abc6983⟩
ISSN: 2375-2548
Popis: MS-derived oligodendrocytes conserve their ability to fully interact with axons and glial cells in vivo.
Remyelination failure in multiple sclerosis (MS) is associated with a migration/differentiation block of oligodendroglia. The reason for this block is highly debated. It could result from disease-related extrinsic or intrinsic regulators in oligodendroglial biology. To avoid confounding immune-mediated extrinsic effect, we used an immune-deficient mouse model to compare induced pluripotent stem cell–derived oligodendroglia from MS and healthy donors following engraftment in the developing CNS. We show that the MS-progeny behaves and differentiates into oligodendrocytes to the same extent as controls. They generate equal amounts of myelin, with bona fide nodes of Ranvier, and promote equal restoration of their host slow conduction. MS-progeny expressed oligodendrocyte- and astrocyte-specific connexins and established functional connections with donor and host glia. Thus, MS oligodendroglia, regardless of major immune manipulators, are intrinsically capable of myelination and making functional axo-glia/glia-glia connections, reinforcing the view that the MS oligodendrocyte differentiation block is not from major intrinsic oligodendroglial deficits.
Databáze: OpenAIRE
Externí odkaz: