Cell Reports (Aug 2017)
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. Bátiz,
- Christer Betsholtz,
- Ludwig Aigner,
- Robin J.M. Franklin,
- Francisco J. Rivera
Affiliations
- Alerie Guzman De La Fuente
- Wellcome Trust and MRC Cambridge Stem Cell Institute, University of Cambridge, Cambridge CB20AH, UK
- Simona Lange
- Institute of Molecular Regenerative Medicine, Paracelsus Medical University Salzburg, 5020 Salzburg, Austria
- Maria Elena Silva
- Wellcome Trust and MRC Cambridge Stem Cell Institute, University of Cambridge, Cambridge CB20AH, UK
- Ginez A. Gonzalez
- Wellcome Trust and MRC Cambridge Stem Cell Institute, University of Cambridge, Cambridge CB20AH, UK
- Herbert Tempfer
- Spinal Cord Injury and Tissue Regeneration Center Salzburg (SCI-TReCS), Paracelsus Medical University Salzburg, 5020 Salzburg, Austria
- Peter van Wijngaarden
- Wellcome Trust and MRC Cambridge Stem Cell Institute, University of Cambridge, Cambridge CB20AH, UK
- Chao Zhao
- Wellcome Trust and MRC Cambridge Stem Cell Institute, University of Cambridge, Cambridge CB20AH, UK
- Ludovica Di Canio
- Wellcome Trust and MRC Cambridge Stem Cell Institute, University of Cambridge, Cambridge CB20AH, UK
- Andrea Trost
- Institute of Molecular Regenerative Medicine, Paracelsus Medical University Salzburg, 5020 Salzburg, Austria
- Lara Bieler
- Spinal Cord Injury and Tissue Regeneration Center Salzburg (SCI-TReCS), Paracelsus Medical University Salzburg, 5020 Salzburg, Austria
- Pia Zaunmair
- Spinal Cord Injury and Tissue Regeneration Center Salzburg (SCI-TReCS), Paracelsus Medical University Salzburg, 5020 Salzburg, Austria
- Peter Rotheneichner
- Spinal Cord Injury and Tissue Regeneration Center Salzburg (SCI-TReCS), Paracelsus Medical University Salzburg, 5020 Salzburg, Austria
- Anna O’Sullivan
- Spinal Cord Injury and Tissue Regeneration Center Salzburg (SCI-TReCS), Paracelsus Medical University Salzburg, 5020 Salzburg, Austria
- Sebastien Couillard-Despres
- Spinal Cord Injury and Tissue Regeneration Center Salzburg (SCI-TReCS), Paracelsus Medical University Salzburg, 5020 Salzburg, Austria
- Oihana Errea
- Wellcome Trust and MRC Cambridge Stem Cell Institute, University of Cambridge, Cambridge CB20AH, UK
- Maarja A. Mäe
- Department of Immunology, Genetics and Pathology, Rudbeck Laboratory, Uppsala University, 751 85 Uppsala, Sweden
- Johanna Andrae
- Department of Immunology, Genetics and Pathology, Rudbeck Laboratory, Uppsala University, 751 85 Uppsala, Sweden
- Liqun He
- Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin Neurological Institute, Key Laboratory of Post-Neuroinjury Neuro-Repair and Regeneration in Central Nervous System, Ministry of Education and Tianjin City, Tianjin 300052, China
- Annika Keller
- Division of Neurosurgery, Zürich University Hospital, Zürich University, 8091 Zürich, Switzerland
- Luis F. Bátiz
- Laboratory of Stem Cells and Neuroregeneration, Institute of Anatomy, Histology and Pathology, Faculty of Medicine, Universidad Austral de Chile, Valdivia, Chile
- Christer Betsholtz
- Department of Immunology, Genetics and Pathology, Rudbeck Laboratory, Uppsala University, 751 85 Uppsala, Sweden
- Ludwig Aigner
- Institute of Molecular Regenerative Medicine, Paracelsus Medical University Salzburg, 5020 Salzburg, Austria
- Robin J.M. Franklin
- Wellcome Trust and MRC Cambridge Stem Cell Institute, University of Cambridge, Cambridge CB20AH, UK
- Francisco J. Rivera
- Wellcome Trust and MRC Cambridge Stem Cell Institute, University of Cambridge, Cambridge CB20AH, UK
- DOI
- https://doi.org/10.1016/j.celrep.2017.08.007
- Journal volume & issue
-
Vol. 20,
no. 8
pp. 1755 – 1764
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.
Keywords
