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 F BátizChrister Betsholtz, Ludwig Aigner, Robin J M Franklin, Francisco J Rivera

Research output: Contribution to journalArticle

42 Citations (Scopus)
5 Downloads (Pure)

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
Publication statusPublished - 22 Aug 2017

Keywords

  • Animals
  • Cell Differentiation/physiology
  • Cells, Cultured
  • Central Nervous System/cytology
  • Demyelinating Diseases
  • Humans
  • Mice
  • Nerve Regeneration/physiology
  • Oligodendroglia/cytology
  • Pericytes/cytology

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  • Cite this

    De La Fuente, A. G., Lange, S., Silva, M. E., Gonzalez, G. A., Tempfer, H., van Wijngaarden, P., Zhao, C., Di Canio, L., Trost, A., Bieler, L., Zaunmair, P., Rotheneichner, P., O'Sullivan, A., Couillard-Despres, S., Errea, O., Mäe, M. A., Andrae, J., He, L., Keller, A., ... Rivera, F. J. (2017). Pericytes Stimulate Oligodendrocyte Progenitor Cell Differentiation during CNS Remyelination. Cell Reports, 20(8), 1755-1764. https://doi.org/10.1016/j.celrep.2017.08.007