Pericytes Stimulate Oligodendrocyte Progenitor Cell Differentiation during CNS Remyelination

Publication date: 22 August 2017
Source:Cell Reports, Volume 20, Issue 8
Author(s): 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 F. Bátiz, Christer Betsholtz, Ludwig Aigner, Robin J.M. Franklin, Francisco J. Rivera
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 Pdgfb^ret/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.

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Teaser

Following toxin-induced demyelination in PC-deficient mice and using a number of in vitro approaches, Guzman de la Fuente et al. show that CNS pericytes (PCs) respond to demyelination and, through Lama2 secretion, stimulate oligodendrocyte progenitor cell differentiation during remyelination. These findings extend PC function beyond vascular homeostasis toward regeneration.


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