biostudies-arrayexpressJan MulderHomo sapienshttps://www.ebi.ac.uk/biostudies/studies/E-MTAB-17040Fresh frozen samples from human white matter MS lesions. Using Stereo-seq we compared mixed active/inactive lesions with lipid-laden foamy microglia with lesions containing ramified microglia. Study includes post-mortem subcortical white matter (WM) tissue of n = 7 donors with MS (5 females, 2 males). Scripts used for analysis are available stored on github under doi: 10.5281/zenodo.19710470biostudies-arrayexpressSequencing - the STOmics Stereo-seq Transcriptomics Set (v1.2)Nucleic Acid Extraction - the STOmics Stereo-seq Transcriptomics Set (v1.2)Library Construction - the STOmics Stereo-seq Transcriptomics Set (v1.2)Sample Collection - Post-mortem subcortical white matter (WM) tissue of n = 7 donors with MS (5 females, 2 males) was obtained from the Netherlands Brain Bank (Amsterdam, The Netherlands, www.brainbank.nl). All donors provided informed consent for brain autopsy and the use of tissue and clinical data for research purposes, in accordance with national ethical guidelines. MS lesions were classified based on microglia state and post-mortem subcortical white matter (WM) mixed lesions with 94 ramified microglia, mixed lesions with foamy microglia, and normal-appearing WM (NAWM) were selected. Cryosectioning of fresh frozen brain tissue at 10 um thickness.MIAME ScoreOrganizationAssays and DataProcessed DataMAGE-TAB FilesSequence Alignment - Gong C et al (2024) SAW: an efficient and accurate data analysis workflow for Stereo-seq spatial transcriptomics. Gigabyte 2024:gigabyte111Data Transformation - Gong C et al (2024) SAW: an efficient and accurate data analysis workflow for Stereo-seq spatial transcriptomics. Gigabyte 2024:gigabyte111UnknownTranscriptomicsGenomicsProteomicsDNBSEQ-T7<h4>Summary paragraph</h4> Multiple sclerosis (MS) is a neuroinflammatory disease of the central nervous system, characterized by demyelinating lesions 1 . Lesion expansion contributes to progression and increased disability, while remyelination can recover neurological deficits. However, mechanisms driving lesion dynamics are largely unclear, hindering the development of effective therapeutics. We propose that distinct states of microglia are involved in lesion expansion and remyelination 2,3 . Using Stereo-seq, an RNA capture based high-resolution spatial transcriptomics technology with single-cell resolution, on post-mortem human brain tissue, we compared mixed active/inactive lesions with lipid-laden foamy microglia with lesions containing ramified microglia. We identified distinct cellular and molecular mechanisms underlying lesion activity and remyelination, linked to microglia phenotypes and states. Lesions with foamy microglia were characterized by elevated immune activation, increased lymphocyte densities, upregulated immunoglobulin production ( IGHG1 , IGHG3 ), increased complement system activity, indication of iron dysregulation ( FTL , FTH1 ), and increased demyelination. In contrast, lesions with ramified microglia exhibited gene expression profiles indicative of myelin stability ( ABCA2 , QKI ) and neuro-axonal protection, fostering an environment conducive to repair and remyelination. Our findings highlight the role of microglial states in lesion expansion and repair in MS and offer promising avenues for the development of therapeutic approaches aimed at preventing MS disability progression.spatial transcriptomics by high-throughput sequencingHomo sapiensMicroglial states determine lesion dynamics in multiple sclerosisAletta M.R. van den Bosch, Jia Hui Khoo, Zhigang Lu, Han Liang, Dennis Wever, Li Pu, Bart J.L. Eggen, Mathias Uhlén, Joost Smolders, Jörg Hamann, Zhouchun Shang, Jan Mulder, Inge HuitingaAletta van den BoschJan MulderfalseStereo-seq analysis of human multiple sclerosis white matter lesionsFresh frozen samples from human white matter MS lesions. Using Stereo-seq we compared mixed active/inactive lesions with lipid-laden foamy microglia with lesions containing ramified microglia. Study includes post-mortem subcortical white matter (WM) tissue of n = 7 donors with MS (5 females, 2 males). Scripts used for analysis are available stored on github under doi: 10.5281/zenodo.197104702026-05-11T00:00:00Z2026-05-13T14:11:51.575Z2026-05-08T13:18:42.913ZE-MTAB-17040EFO_0002944EFO_0004170EFO_0030005EFO_0004917EFO_0005518EFO_0003816EFO_000418410.1101/2024.10.25.620251