Distinct transcriptomic and epigenomic responses of mature oligodendrocytes during disease progression in a mouse model of multiple sclerosis

Zheng, Chao; Hervé, Bastien; Meijer, Mandy; Rubio Rodríguez-Kirby, Leslie Ann; Guerreiro Cacais, André Ortlieb; Kukanja, Petra; Kabbe, Mukund; Jimenez-Beristain, Tony; Olsson, Tomas; Agirre, Eneritz; Castelo-Branco, Gonçalo

Distinct transcriptomic and epigenomic responses of mature oligodendrocytes during disease progression in a mouse model of multiple sclerosis

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Item Type:	Article
Title:	Distinct transcriptomic and epigenomic responses of mature oligodendrocytes during disease progression in a mouse model of multiple sclerosis
Creators Name:	Zheng, Chao, Hervé, Bastien, Meijer, Mandy, Rubio Rodríguez-Kirby, Leslie Ann, Guerreiro Cacais, André Ortlieb, Kukanja, Petra, Kabbe, Mukund, Jimenez-Beristain, Tony, Olsson, Tomas, Agirre, Eneritz and Castelo-Branco, Gonçalo
Abstract:	Multiple sclerosis (MS) is a chronic autoimmune disease that targets mature oligodendrocytes (MOLs) and their myelin. MOLs are heterogeneous and can transition to immune-like states in MS. However, the dynamics of this process remain unclear. Here, we used single-cell multiome assay for transposase-accessible chromatin and RNA sequencing targeting oligodendroglia (OLG) from the experimental autoimmune encephalomyelitis (EAE) MS mouse model at multiple disease stages. We found that immune OLG states appear at early disease stages and persist to late stages, which can be consistent with epigenetic memory of previous neuroinflammation. Transcription factor activity suggested immunosuppression in OLG at early disease stages. Different MOLs exhibit differential responsiveness to EAE, with MOL2 exhibiting a stronger transcriptional immune response than MOL5/MOL6, and showed divergent responses at the epigenetic level during disease evolution. Our single-cell multiomic resource highlights dynamic and subtype-specific responses of OLG to EAE, which might be amenable to modulation in MS.
Source:	Nature Neuroscience
ISSN:	1097-6256
Publisher:	Nature Publishing Group
Date:	17 November 2025
Official Publication:	https://doi.org/10.1038/s41593-025-02100-3
PubMed:	View item in PubMed
Related to:	URL URL Type https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE250589 External Dataset https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE283085 External Dataset https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE283086 External Dataset https://olg-dyn-eae-multiome.cells.ucsc.edu/ External Dataset https://ki.se/en/research/research-areas-centres-and-networks/research-groups/goncalo-castelo-branco-group#tab-oligointernode-datasets-and-resources External Dataset http://github.com/Castelo-Branco-lab/EAE_multiomics_2025 Software

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