Claire L. Davies and Veronique E. Miron Centre for Reproductive Health, University of Edinburgh, Edinburgh, UKThe regeneration of myelin (remyelination) in the central nervous system is impaired in progressive multiple sclerosis. This highlights the need to understand the cellular and molecular mechanisms underpinning efficient remyelination in order to develop effective pro-remyelination therapies. Our previous work implicated microglia and infiltrating monocyte-derived macrophages in regulating the oligodendrocyte progenitor cell responses during remyelination. Here we further investigated the role of microglia/ macrophages in this process by analysing the transcriptome of each population throughout remyelination in vivo using RNA sequencing. We isolated microglia (Cd11b+ Cd45lo) and monocyte-derived macrophages (Cd11b+Cd45hi) from focal demyelinated lesions of the adult mouse corpus callosum at different stages of the remyelination process. To understand the influence of infiltrating monocyte-derived macrophages on microglia gene expression, we also compared transcriptomes of cells extracted from wildtype mice versus CCR2-/- mice, in which inflammatory monocytes are excluded from the lesion site.These data reveal that during remyelination, microglia and monocyte-derived macrophages show differential expression of genes and pathways at distinct stages of the regenerative process, and the influence of infiltrating monocyte-derived macrophages on microglial gene expression. Our data provides evidence for potential therapeutic targets on microglia and monocyte-derived macrophages to promote efficient remyelination.Funded by: This article was published on 2024-12-13
