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Injury-induced perivascular niche supports alternative differentiation of adult rodent CNS progenitor cells

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 involv...

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Autores principales: Ulanska-Poutanen, Justyna, Mieczkowski, Jakub, Zhao, Chao, Konarzewska, Katarzyna, Kaza, Beata, Pohl, Hartmut BF, Bugajski, Lukasz, Kaminska, Bozena, Franklin, Robin JM, Zawadzka, Malgorzata
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6141235/
https://www.ncbi.nlm.nih.gov/pubmed/30222103
http://dx.doi.org/10.7554/eLife.30325
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author Ulanska-Poutanen, Justyna
Mieczkowski, Jakub
Zhao, Chao
Konarzewska, Katarzyna
Kaza, Beata
Pohl, Hartmut BF
Bugajski, Lukasz
Kaminska, Bozena
Franklin, Robin JM
Zawadzka, Malgorzata
author_facet Ulanska-Poutanen, Justyna
Mieczkowski, Jakub
Zhao, Chao
Konarzewska, Katarzyna
Kaza, Beata
Pohl, Hartmut BF
Bugajski, Lukasz
Kaminska, Bozena
Franklin, Robin JM
Zawadzka, Malgorzata
author_sort Ulanska-Poutanen, Justyna
collection PubMed
description 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 non-vascular 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.
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spelling pubmed-61412352018-09-20 Injury-induced perivascular niche supports alternative differentiation of adult rodent CNS progenitor cells Ulanska-Poutanen, Justyna Mieczkowski, Jakub Zhao, Chao Konarzewska, Katarzyna Kaza, Beata Pohl, Hartmut BF Bugajski, Lukasz Kaminska, Bozena Franklin, Robin JM Zawadzka, Malgorzata eLife Neuroscience 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 non-vascular 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. eLife Sciences Publications, Ltd 2018-09-17 /pmc/articles/PMC6141235/ /pubmed/30222103 http://dx.doi.org/10.7554/eLife.30325 Text en © 2018, Ulanska-Poutanen et al http://creativecommons.org/licenses/by/4.0/ http://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Neuroscience
Ulanska-Poutanen, Justyna
Mieczkowski, Jakub
Zhao, Chao
Konarzewska, Katarzyna
Kaza, Beata
Pohl, Hartmut BF
Bugajski, Lukasz
Kaminska, Bozena
Franklin, Robin JM
Zawadzka, Malgorzata
Injury-induced perivascular niche supports alternative differentiation of adult rodent CNS progenitor cells
title Injury-induced perivascular niche supports alternative differentiation of adult rodent CNS progenitor cells
title_full Injury-induced perivascular niche supports alternative differentiation of adult rodent CNS progenitor cells
title_fullStr Injury-induced perivascular niche supports alternative differentiation of adult rodent CNS progenitor cells
title_full_unstemmed Injury-induced perivascular niche supports alternative differentiation of adult rodent CNS progenitor cells
title_short Injury-induced perivascular niche supports alternative differentiation of adult rodent CNS progenitor cells
title_sort injury-induced perivascular niche supports alternative differentiation of adult rodent cns progenitor cells
topic Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6141235/
https://www.ncbi.nlm.nih.gov/pubmed/30222103
http://dx.doi.org/10.7554/eLife.30325
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