Cell type mapping reveals tissue niches and interactions in subcortical multiple sclerosis lesions.

Autor: Lerma-Martin C; Department of Neurology, Division of Neuroimmunology, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany., Badia-I-Mompel P; Institute for Computational Biomedicine, Faculty of Medicine, Heidelberg University and Heidelberg University Hospital, Heidelberg, Germany.; GSK, Cellzome, Heidelberg, Germany.; European Molecular Biology Laboratory, European Bioinformatics Institute (EMBL-EBI), Hinxton, UK., Ramirez Flores RO; Institute for Computational Biomedicine, Faculty of Medicine, Heidelberg University and Heidelberg University Hospital, Heidelberg, Germany.; European Molecular Biology Laboratory, European Bioinformatics Institute (EMBL-EBI), Hinxton, UK., Sekol P; Department of Neurology, Division of Neuroimmunology, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany., Schäfer PSL; Institute for Computational Biomedicine, Faculty of Medicine, Heidelberg University and Heidelberg University Hospital, Heidelberg, Germany.; European Molecular Biology Laboratory, European Bioinformatics Institute (EMBL-EBI), Hinxton, UK., Riedl CJ; Department of Neurology, Division of Neuropathology and Neurochemistry, Medical University of Vienna, Vienna, Austria.; Comprehensive Center for Clinical Neurosciences and Mental Health, Medical University of Vienna, Vienna, Austria., Hofmann A; Department of Neurology, Division of Neuroimmunology, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany., Thäwel T; Department of Neurology, Division of Neuroimmunology, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany., Wünnemann F; Institute for Computational Biomedicine, Faculty of Medicine, Heidelberg University and Heidelberg University Hospital, Heidelberg, Germany., Ibarra-Arellano MA; Institute for Computational Biomedicine, Faculty of Medicine, Heidelberg University and Heidelberg University Hospital, Heidelberg, Germany., Trobisch T; Department of Neurology, Division of Neuroimmunology, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany., Eisele P; Department of Neurology, Division of Neuroimmunology, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.; Mannheim Center for Translational Neuroscience, Medical Faculty, Mannheim Heidelberg University, Mannheim, Germany., Schapiro D; Institute for Computational Biomedicine, Faculty of Medicine, Heidelberg University and Heidelberg University Hospital, Heidelberg, Germany.; Institute of Pathology, Faculty of Medicine, Heidelberg University and Heidelberg University Hospital, Heidelberg, Germany.; Translational Spatial Profiling Center (TSPC), Heidelberg, Germany., Haeussler M; Genomics Institute, University of California Santa Cruz, Santa Cruz, CA, USA., Hametner S; Department of Neurology, Division of Neuropathology and Neurochemistry, Medical University of Vienna, Vienna, Austria.; Comprehensive Center for Clinical Neurosciences and Mental Health, Medical University of Vienna, Vienna, Austria., Saez-Rodriguez J; Institute for Computational Biomedicine, Faculty of Medicine, Heidelberg University and Heidelberg University Hospital, Heidelberg, Germany. pub.saez@uni-heidelberg.de.; European Molecular Biology Laboratory, European Bioinformatics Institute (EMBL-EBI), Hinxton, UK. pub.saez@uni-heidelberg.de., Schirmer L; Department of Neurology, Division of Neuroimmunology, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany. lucas.schirmer@medma.uni-heidelberg.de.; Mannheim Center for Translational Neuroscience, Medical Faculty, Mannheim Heidelberg University, Mannheim, Germany. lucas.schirmer@medma.uni-heidelberg.de.; Interdisciplinary Center for Neurosciences, Heidelberg University, Heidelberg, Germany. lucas.schirmer@medma.uni-heidelberg.de.
Jazyk: angličtina
Zdroj: Nature neuroscience [Nat Neurosci] 2024 Dec; Vol. 27 (12), pp. 2354-2365. Date of Electronic Publication: 2024 Nov 05.
DOI: 10.1038/s41593-024-01796-z
Abstrakt: 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.
Competing Interests: Competing interests: P.E. has received travel expenses from Bayer Health Care. D.S. reports funding from Cellzome, a GSK company and received honorariums from Immunai, Noetik, Alpenglow and Lunaphore. J.S.-R. reports funding from GSK, Pfizer and Sanofi and fees/honoraria from Travere Therapeutics, Stadapharm, Astex, Owkin, Moderna, Pfizer and Grunenthal. L.S. reports research support from Roche and Merck and filed a patent for the detection of antibodies against KIR4.1 in a subpopulation of patients with multiple sclerosis (WO2015166057A1). The remaining authors declare no competing interests.
(© 2024. The Author(s).)
Databáze: MEDLINE
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