Dataset Information

Pericytes Stimulate Oligodendrocyte Progenitor Cell Differentiation during CNS Remyelination.

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 Pdgfb^ret/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.

SUBMITTER: De La Fuente AG

PROVIDER: S-EPMC5574064 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature

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Publications

Pericytes Stimulate Oligodendrocyte Progenitor Cell Differentiation during CNS Remyelination.

De La Fuente Alerie Guzman AG Lange Simona S Silva Maria Elena ME Gonzalez Ginez A GA Tempfer Herbert H van Wijngaarden Peter P Zhao Chao C Di Canio Ludovica L Trost Andrea A Bieler Lara L Zaunmair Pia P Rotheneichner Peter P O'Sullivan Anna A Couillard-Despres Sebastien S Errea Oihana O Mäe Maarja A MA Andrae Johanna J He Liqun L Keller Annika A Bátiz Luis F LF Betsholtz Christer C Aigner Ludwig L Franklin Robin J M RJM Rivera Francisco J FJ

Cell reports 20170801 8

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 Pdgfb<sup>ret/ret</sup> mice, which have reduced PC numbers, oligodendrocyte progenitor cell (OPC) differentiation was delayed, although remyelination proceeded to ...[more]

PMID: 28834740

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Project description:We used transcription-profiling to identify mitogen-activated protein kinase (Mapk) signaling as an important regulator involved in the differentiation of oligodendrocyte progenitor cells (OPCs) into oligodendrocytes. We show in tissue culture that activation of Mapk signaling by elevation of intracellular levels of cAMP using administration of either dibutyryl-cAMP or inhibitors of the cAMP-hydrolyzing enzyme phosphodiesterase-4 (Pde4) enhances OPC differentiation. Finally, we demonstrate that systemic delivery of a Pde4 inhibitor leads to enhanced differentiation of OPCs within focal areas of toxin-induced demyelination and a consequent acceleration of remyelination. Study was conducted to identify the genes that are differentialy regulated during early time point of OPC differentiation. This study includes reanalyzed data from the following 6 Samples available in GSE24821: [i] 5 days post lesion (dpl) laser captured caudal cerebellar peduncle (CCP) replicates 1-3 (GSM610956-GSM610958), and [ii] 14 dpl laser captured CCP replicates 1-3 (GSM610959-GSM610961). For the reanalyzed data, raw data files were background-corrected, normalized and summarized using the RMA algorithm as implemented in the R statistical programming environment (http://www.r-project.org). Differential expression between sample groups was assessed using the moderated t-test as implemented in the limma package for the Bioconductor suite of R bioinformatics software (http://bioconductor.org). In order to correct for hypothesis testing on such a scale, P-values relating to differential expression were corrected for multiple testing using FDR correction. Differential expression across sample groups was deemed significant at an FDR of 5% (q < 0.05). The processed data for the reanalyzed dataset is linked below as supplementary file 'GSE50042_reanalyzed_Samples.txt'. The processed data for Samples GSM1213100-GSM1213114 is linked below as supplementary file 'GSE50042_processed_data.txt'.

Dataset Information

Pericytes Stimulate Oligodendrocyte Progenitor Cell Differentiation during CNS Remyelination.

Publications

Pericytes Stimulate Oligodendrocyte Progenitor Cell Differentiation during CNS Remyelination.

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