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@MISC{Liu:282302,
author = {Liu, Qian},
title = {{D}ataset: {M}olecular and spatial profiling of multiple
sclerosis lesions identifies dysfunctional lipid efflux as a
driver of chronic active inflammation},
reportid = {DZNE-2025-01272},
year = {2025},
abstract = {Compartmentalized 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.},
cin = {AG Latz},
cid = {I:(DE-2719)1013024},
pnm = {351 - Brain Function (POF4-351)},
pid = {G:(DE-HGF)POF4-351},
typ = {PUB:(DE-HGF)32},
url = {https://pub.dzne.de/record/282302},
}