Journal article
Pericytes Stimulate Oligodendrocyte Progenitor Cell Differentiation during CNS Remyelination
AG De La Fuente, S Lange, ME Silva, GA Gonzalez, H Tempfer, P van Wijngaarden, C Zhao, L Di Canio, A Trost, L Bieler, P Zaunmair, P Rotheneichner, A O'Sullivan, S Couillard-Despres, O Errea, MA Mäe, J Andrae, L He, A Keller, LF Bátiz Show all
Cell Reports | CELL PRESS | Published : 2017
Abstract
The role of the neurovascular niche in CNS myelin regeneration is incompletely understood. Here, we show that, upon demyelination, CNS-resident pericytes (PCs) proliferate, and parenchymal non-vessel-associated PC-like cells (PLCs) rapidly develop. During remyelination, mature oligodendrocytes were found in close proximity to PCs. In Pdgfbret/ret mice, which have reduced PC numbers, oligodendrocyte progenitor cell (OPC) differentiation was delayed, although remyelination proceeded to completion. PC-conditioned medium accelerated and enhanced OPC differentiation in vitro and increased the rate of remyelination in an ex vivo cerebellar slice model of demyelination. We identified Lama2 as a PC-..
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Grants
Awarded by Stiftung Synapsis - Alzheimer Forschung Schweiz AFS
Funding Acknowledgements
We thank Hannelore Bauer, Peter Hammerl, and Andreas Traweger for technical advice and support. This work was supported by research funds from Chilean FONDECYT Program CONICYT Grants 1161787 (to F.J.R.) and 1141015 (to L.F.B); Direccion de Investigacion y Desarrollo-Universidad Austral de Chile (DID-UACh); Paracelsus Medical University PMU-FFF Long-Term Fellowship L-12/01/001-RIV (to F.J.R.) and Stand-Alone Grant E-12/15/077-RIT (to F.J.R. and A.T.); the European Union Seventh Framework Program (FP7/2007-2013) under Grant Agreements HEALTH-F2-2011-278850 (INMiND), HEALTH-F2-2011-279288 (IDEA), and FP7-REGPOT-316120 (GlowBrain); Austrian Science Fund FWF Special Research Program (SFB) F44 (F4413-B23) "Cell Signaling in Chronic CNS Disorders''; and State Government of Salzburg, Austria (Stiftungsprofessur and 20204-WISS/80/199-2014). In addition, this study was supported by grants from a core support grant from the Wellcome Trust (203151/Z/16/Z) and MRC to the Wellcome Trust-Medical Research Council Cambridge Stem Cell Institute, the UK Multiple Sclerosis Society (941/11), the David and Isobel Walker Trust, "Investissements d'avenir'' IHU-A-ICM and Obra Social La Caixa, the Swedish Science Council (2015-00550), the Swedish Cancer Foundation (15 0735), the Knut and Alice Wallenberg Foundation (2015.0030), the European Research Council (AdG 294556 BBBARRIER), and the Leducq Foundation (Sphingonet; 14CVD02). P.v.W. was supported by National Health & Medical Research Council of Australia Early Career Fellowship 628928. Work in A.K.'s group was funded by the Swiss National Science Foundation (31003A_159514/1; http://www.snf.ch/en) and The Synapsis Foundation (http://www.alzheimer-synapsis.ch).