TY - JOUR
T1 - Pericytes Stimulate Oligodendrocyte Progenitor Cell Differentiation during CNS Remyelination
AU - De La Fuente, Alerie Guzman
AU - Lange, Simona
AU - Silva, Maria Elena
AU - Gonzalez, Ginez A.
AU - Tempfer, Herbert
AU - van Wijngaarden, Peter
AU - Zhao, Chao
AU - Di Canio, Ludovica
AU - Trost, Andrea
AU - Bieler, Lara
AU - Zaunmair, Pia
AU - Rotheneichner, Peter
AU - O'Sullivan, Anna
AU - Couillard-Despres, Sebastien
AU - Errea, Oihana
AU - Mäe, Maarja A.
AU - Andrae, Johanna
AU - He, Liqun
AU - Keller, Annika
AU - Bátiz, Luis F.
AU - Betsholtz, Christer
AU - Aigner, Ludwig
AU - Franklin, Robin J.M.
AU - Rivera, Francisco J.
N1 - 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
PY - 2017/8/22
Y1 - 2017/8/22
N2 - 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.
AB - 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.
KW - Lama2
KW - neurovascular niche
KW - oligodendrocyte progenitor cell
KW - pericytes
KW - remyelination
KW - Lama2
KW - Nicho neurovascular
KW - Célula progenitora de oligodendrocitos
KW - Remielinización
UR - http://www.scopus.com/inward/record.url?scp=85028296852&partnerID=8YFLogxK
U2 - 10.1016/j.celrep.2017.08.007
DO - 10.1016/j.celrep.2017.08.007
M3 - Article
C2 - 28834740
AN - SCOPUS:85028296852
SN - 2211-1247
VL - 20
SP - 1755
EP - 1764
JO - Cell Reports
JF - Cell Reports
IS - 8
ER -