Pericytes Stimulate Oligodendrocyte Progenitor Cell Differentiation during CNS Remyelination

Alerie Guzman De La Fuente, Simona Lange, Maria Elena Silva, Ginez A. Gonzalez, Herbert Tempfer, Peter van Wijngaarden, Chao Zhao, Ludovica Di Canio, Andrea Trost, Lara Bieler, Pia Zaunmair, Peter Rotheneichner, Anna O'Sullivan, Sebastien Couillard-Despres, Oihana Errea, Maarja A. Mäe, Johanna Andrae, Liqun He, Annika Keller, Luis Federico BatizChrister Betsholtz, Ludwig Aigner, Robin J.M. Franklin, Francisco J. Rivera

Research output: Contribution to journalArticlepeer-review

51 Scopus citations

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-derived factor that promotes OPC differentiation. Thus, the functional role of PCs is not restricted to vascular homeostasis but includes the modulation of adult CNS progenitor cells involved in regeneration.

Original languageEnglish
Pages (from-to)1755-1764
Number of pages10
JournalCell Reports
Volume20
Issue number8
DOIs
StatePublished - 22 Aug 2017

Bibliographical note

Funding Information:
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 Investigación 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 ).

Publisher Copyright:
© 2017 The Authors

Keywords

  • Lama2
  • neurovascular niche
  • oligodendrocyte progenitor cell
  • pericytes
  • remyelination

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