Injury-induced perivascular niche supports alternative differentiation of adult rodent CNS progenitor cells.
eLife Sciences Publications Ltd
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Ulanska-Poutanen, J., Mieczkowski, J., Zhao, C., Konarzewska, K., Kaza, B., Pohl, H. B., Bugajski, L., et al. (2018). Injury-induced perivascular niche supports alternative differentiation of adult rodent CNS progenitor cells.. eLife, 7 https://doi.org/10.7554/elife.30325
Following CNS demyelination, oligodendrocyte progenitor cells (OPCs) are able to differentiate into either remyelinating oligodendrocytes (OLs) or remyelinating Schwann cells (SCs). However, the signals that determine which type of remyelinating cell is generated and the underlying mechanisms involved have not been identified. Here, we show that distinctive microenvironments created in discrete niches within demyelinated white matter determine fate decisions of adult OPCs. By comparative transcriptome profiling we demonstrate that an ectopic, injury-induced perivascular niche is enriched with secreted ligands of the BMP and Wnt signalling pathways, produced by activated OPCs and endothelium, whereas reactive astrocyte within nonvascular area express the dual BMP/Wnt antagonist Sostdc1. The balance of BMP/Wnt signalling network is instructive for OPCs to undertake fate decision shortly after their activation: disruption of the OPCs homeostasis during demyelination results in BMP4 upregulation, which, in the absence of Socstdc1, favours SCs differentiation.
Central Nervous System, Astrocytes, Oligodendroglia, Peripheral Nervous System, Endothelial Cells, Stem Cells, Animals, Rats, Demyelinating Diseases, Wounds and Injuries, Bone Morphogenetic Proteins, RNA, Messenger, Ligands, Cell Differentiation, Gene Expression Regulation, Stem Cell Niche, Wnt Signaling Pathway, Cellular Microenvironment
This work was funded by the National Science Centre grants, NN 401 584238 (MZ) and 2012/07/N/ NZ3/01943 (JU-P), a programme grant from the UK Multiple Sclerosis Society (RJMF, CZ) and a core support grant from the Wellcome Trust and MRC to the Wellcome Trust – Medical Research Council Cambridge Stem Cell Institute (RJMF).
External DOI: https://doi.org/10.7554/elife.30325
This record's URL: https://www.repository.cam.ac.uk/handle/1810/285445
Attribution 4.0 International
Licence URL: https://creativecommons.org/licenses/by/4.0/