4D marmoset brain map reveals MRI and molecular signatures for onset of multiple sclerosis-like lesions

• 成果类型: Article
• 署名作者: Lin, Jing-Ping; Brake, Alexis; Donadieu, Maxime; Lee, Amanda; Smith, Ginger; Hu, Kevin; Nair, Govind; Kawaguchi, Riki; Sati, Pascal; Geschwind, Daniel H.; Jacobson, Steven; Schafer, Dorothy P.; Reich, Daniel S.
• 署名单位: National Institutes of Health (NIH) - USA; NIH National Institute of Neurological Disorders & Stroke (NINDS); University of California System; University of California Los Angeles; University of California Los Angeles Medical Center; David Geffen School of Medicine at UCLA; University of California System; University of California Los Angeles; University of California System; University of California Los Angeles; Cedars Sinai Medical Center; National Institutes of Health (NIH) - USA; NIH National Institute of Neurological Disorders & Stroke (NINDS); University of Massachusetts System; UMass Chan Medical School; University of Massachusetts Worcester
• 刊物名称: SCIENCE
• ISSN/ISSBN: 0036-8109
• DOI: 10.1126/science.adp6325
• 发表日期: 2025-02-28
• 关键词: growth-factor; autoimmune encephalomyelitis; common marmosets; expression; autophagy; receptor; peptide; cells; differentiation; Visualization

摘要

Inferring cellular and molecular dynamics of multiple sclerosis (MS) lesions from postmortem tissue collected decades after onset is challenging. Using magnetic resonance image (MRI)-guided spatiotemporal RNA profiling in marmoset experimental autoimmune encephalitis (EAE), we mapped lesion dynamics and modeled molecular perturbations relevant to MS. Five distinct lesion microenvironments emerged, involving neuroglial responses, tissue destruction and repair, and brain border regulation. Before demyelination, MRI identified a high ratio of proton density-weighted signal to T1 relaxation time, capturing early hypercellularity, and elevated astrocytic and ependymal senescence signals marked perivascular and periventricular areas that later became demyelination hotspots. As lesions expanded, concentric glial barriers formed, initially dominated by proliferating and diversifying microglia and oligodendrocyte precursors, later replaced by monocytes and lymphocytes. We highlight SERPINE1+ astrocytes as a signaling hub underlying lesion onset in both marmoset EAE and MS.