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Cell 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 chro...

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Main Authors: Lerma Martin, Celia (Author) , Badia-i-Mompel, Pau (Author) , Ramirez Flores, Ricardo O. (Author) , Sekol, Patricia (Author) , Schäfer, Philipp (Author) , Riedl, Christian J. (Author) , Hofmann, Annika (Author) , Thäwel, Thomas (Author) , Wünnemann, Florian (Author) , Ibarra-Arellano, Miguel A. (Author) , Trobisch, Tim (Author) , Eisele, Philipp (Author) , Schapiro, Denis (Author) , Haeussler, Maximilian (Author) , Hametner, Simon (Author) , Sáez Rodríguez, Julio (Author) , Schirmer, Lucas (Author)
Format: Article (Journal)
Language:English
Published: December 2024
In: Nature neuroscience
Year: 2024, Volume: 27, Issue: 12, Pages: 2354-2365
ISSN:1546-1726
DOI:10.1038/s41593-024-01796-z
Online Access:Verlag, kostenfrei, Volltext: https://doi.org/10.1038/s41593-024-01796-z
Verlag, kostenfrei, Volltext: http://www.nature.com/articles/s41593-024-01796-z
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Author Notes:Celia Lerma-Martin, Pau Badia-i-Mompel, Ricardo O. Ramirez Flores, Patricia Sekol, Philipp S.L. Schäfer, Christian J. Riedl, Annika Hofmann, Thomas Thäwel, Florian Wünnemann, Miguel A. Ibarra-Arellano, Tim Trobisch, Philipp Eisele, Denis Schapiro, Maximilian Haeussler, Simon Hametner, Julio Saez-Rodriguez and Lucas Schirmer
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Summary: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 communication events between myeloid, endothelial and glial cell types. Our results provide insight into the cellular composition, multicellular programs and intercellular communication in tissue niches along the conversion from a homeostatic to a dysfunctional state underlying lesion progression in MS.
Item Description:Online veröffentlicht: 5. November 2024
Gesehen am 14.04.2025
Physical Description:Online Resource
ISSN:1546-1726
DOI:10.1038/s41593-024-01796-z

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