000282302 001__ 282302
000282302 005__ 20251117100924.0
000282302 037__ $$aDZNE-2025-01272
000282302 1001_ $$0P:(DE-2719)9002904$$aLiu, Qian$$b0$$udzne
000282302 245__ $$aDataset: Molecular and spatial profiling of multiple sclerosis lesions identifies dysfunctional lipid efflux as a driver of chronic active inflammation
000282302 260__ $$c2025
000282302 3367_ $$2BibTeX$$aMISC
000282302 3367_ $$0PUB:(DE-HGF)32$$2PUB:(DE-HGF)$$aDataset$$bdataset$$mdataset$$s1763370457_17166
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000282302 3367_ $$2DataCite$$aDataset
000282302 3367_ $$2ORCID$$aDATA_SET
000282302 3367_ $$2DINI$$aResearchData
000282302 520__ $$aCompartmentalized inflammation is considered a critical factor in driving the progression of multiple sclerosis (MS). Yet, the mechanisms sustaining its persistence remain poorly understood. A hallmark of this persistent and slowly evolving inflammatory process are chronic active MS lesions. In this study, we created a high-resolution, single-cell molecular and spatial atlas of chronic inflammation in MS. To accomplish this, we combined single-nucleus RNA sequencing (snRNA-seq) with single-cell spatial transcriptomics using multiplexed error-robust fluorescence in situ hybridization (MERFISH) to examine MS lesions, specifically focusing on those exhibiting chronic active immune pathology characterized by lymphocyte presence. Our integrative profiling uncovered the molecular landscape of glial and immune cells, their disease-associated states, and the surrounding microenvironments. Within the lesion rim, we identified CD8+ T cell niches with lipid-associated microglia. To demonstrate the utility of this spatially resolved atlas of chronic active MS lesions as a resource for future discovery, we investigated the role of lipid-associated microglia in experimental autoimmune encephalomyelitis (EAE). Our findings showed that inhibiting cholesterol efflux increased the formation of lipid-storing phagocytes, "foamy microglia," which actively drive inflammatory processes in EAE and represent tractable therapeutic targets for pharmacological modulators of sterol metabolism. These results provide a framework for system-level insights into cell-type diversity and represent a valuable resource for advancing the study of neuroinflammation in MS.
000282302 536__ $$0G:(DE-HGF)POF4-351$$a351 - Brain Function (POF4-351)$$cPOF4-351$$fPOF IV$$x0
000282302 8564_ $$uhttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE301824
000282302 9101_ $$0I:(DE-588)1065079516$$6P:(DE-2719)9002904$$aDeutsches Zentrum für Neurodegenerative Erkrankungen$$b0$$kDZNE
000282302 9131_ $$0G:(DE-HGF)POF4-351$$1G:(DE-HGF)POF4-350$$2G:(DE-HGF)POF4-300$$3G:(DE-HGF)POF4$$4G:(DE-HGF)POF$$aDE-HGF$$bGesundheit$$lNeurodegenerative Diseases$$vBrain Function$$x0
000282302 9201_ $$0I:(DE-2719)1013024$$kAG Latz$$lInnate Immunity in Neurodegeneration$$x0
000282302 980__ $$adataset
000282302 980__ $$aEDITORS
000282302 980__ $$aVDBINPRINT
000282302 980__ $$aI:(DE-2719)1013024
000282302 980__ $$aUNRESTRICTED