3 years ago

Pericytes Stimulate Oligodendrocyte Progenitor Cell Differentiation during CNS Remyelination

Pericytes Stimulate Oligodendrocyte Progenitor Cell Differentiation during CNS Remyelination
Maria Elena Silva, Herbert Tempfer, Francisco J. Rivera, Lara Bieler, Maarja A. Mäe, Sebastien Couillard-Despres, Pia Zaunmair, Alerie Guzman De La Fuente, Luis F. Bátiz, Liqun He, Ludwig Aigner, Christer Betsholtz, Oihana Errea, Annika Keller, Simona Lange, Peter van Wijngaarden, Andrea Trost, Johanna Andrae, Anna O’Sullivan, Ginez A. Gonzalez, Robin J.M. Franklin, Chao Zhao, Ludovica Di Canio, Peter Rotheneichner

Summary

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.

Publisher URL: http://www.cell.com/cell-reports/fulltext/S2211-1247(17)31095-1

DOI: 10.1016/j.celrep.2017.08.007

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