Extended Data Fig. 8: Molecular profile of subsets of microglia during multiple sclerosis.

a, t-SNE plots representing the core signature genes for lymphocytes (TRAC, TRBC2, CD52 and IL32), myeloid cells (ITGAM, MS4A6A, TYROBP and CD14) and monocytes (CCR2, PLAC8, CLEC12A and FCN1) in the brains of patients with multiple sclerosis. Colour keys reflect the expression levels. b–f, t-SNE plots of genes that are enriched in clusters Hu-C5 to Hu-C7 (b), Hu-C2 (c), Hu-C3 (d), Hu-C4 (e) and Hu-C8 (f) are shown (1,602 microglia cells). Colour codes represent expression levels. g, t-SNE plots depicting genes that are upregulated in the clusters Hu-C2, Hu-C3 and Hu-C8. Colour codes represent expression levels. h, t-SNE plots of genes that were upregulated in the disease-associated subsets of microglia in the mouse demyelination model, but not in the microglia in the brains of patients with multiple sclerosis. Colour codes represent expression levels. i, Immunofluorescence images for TMEM119 and IBA1 in healthy brains or the brains of patients with multiple sclerosis. Arrowheads indicate TMEM119⁺IBA1⁺ cells (filled) in the healthy brains, and TMEM119⁻IBA1⁺ microglia (open) during multiple sclerosis. Representative images out of four mice investigated, per condition, are shown. Scale bar, 50 μm. j, Representative immunofluorescence images for IBA1⁺MRP14⁻ (indicating microglia) and IBA1⁺MRP14⁺ cells (representing infiltrating early activated monocytes) in the healthy brain and brains of patients with multiple sclerosis. Insets show microglia (top row) and monocytes (bottom row) in the multiple-sclerosis lesion. Right, quantification. Bars represent means ± s.e.m. (n = 4 for each condition). Each symbol represents one patient. Scale bars, 50 μm (overview), 4 μm (inset).