biostudies-literatureLerma-Martin CU.S. Department of Health & Human Services | NIH | National Institute of Mental Health (NIMH)European Research CouncilDeutsche Forschungsgemeinschaft (German Research Foundation)NIMH NIH HHSU.S. Department of Health & Human Services | NIH | National Institute of Neurological Disorders and Stroke (NINDS)U.S. Department of Health & Human Services | NIH | National Human Genome Research Institute (NHGRI)NHGRI NIH HHSNINDS NIH HHSNational Multiple Sclerosis Society (National MS Society)Gemeinnützige Hertie-Stiftung (Hertie Foundation)California Institute for Regenerative Medicine (CIRM)2354-2365https://www.ebi.ac.uk/biostudies/studies/S-EPMC11614744biostudies-literatureUnknown27(12)Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system. Inflammation is gradually compartmentalized and restricted to specific tissue niches such as the lesion rim. However, the precise cell type composition of such niches, their interactions and changes between chronic active and inactive stages are incompletely understood. We used single-nucleus and spatial transcriptomics from subcortical MS and corresponding control tissues to map cell types and associated pathways to lesion and nonlesion areas. We identified niches such as perivascular spaces, the inflamed lesion rim or the lesion core that are associated with the glial scar and a cilia-forming astrocyte subtype. Focusing on the inflamed rim of chronic active lesions, we uncovered cell-cell communicatiNature neuroscienceCell type mapping reveals tissue niches and interactions in subcortical multiple sclerosis lesions.PMC11614744SPP 2395, SCHI 1330/2-1, 4-1, and 11-1PA-2002-36405ERC StG, No 950584RF1 MH132662DISC0-14514PA-2002-36405, RFA-2203-39300U24 HG002371U24HG002371R01NS114227RF1MH132662P1180016950584SPP 2395R01 NS114227Ramirez Flores ROEisele PSchirmer LSchafer PSLHaeussler MSaez-Rodriguez JThawel TRiedl CJLerma-Martin CSekol PHametner SBadia-I-Mompel PWunnemann FTrobisch TIbarra-Arellano MASchapiro DHofmann AfalseCell type mapping reveals tissue niches and interactions in subcortical multiple sclerosis lesions.Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system. Inflammation is gradually compartmentalized and restricted to specific tissue niches such as the lesion rim. However, the precise cell type composition of such niches, their interactions and changes between chronic active and inactive stages are incompletely understood. We used single-nucleus and spatial transcriptomics from subcortical MS and corresponding control tissues to map cell types and associated pathways to lesion and nonlesion areas. We identified niches such as perivascular spaces, the inflamed lesion rim or the lesion core that are associated with the glial scar and a cilia-forming astrocyte subtype. Focusing on the inflamed rim of chronic active lesions, we uncovered cell-cell communicati2024-01-01T00:00:00Z2024 Dec2026-04-17T13:09:01.677Z2025-04-04T01:58:06.015ZS-EPMC116147443950103610.1038/s41593-024-01796-z