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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},
}