Fig. 6: Microglial dynamics in the primary focal and distal lesion-like compartments.

a, Schematic of the analysis workflow. b, Cell types^30,56 predicted by cell2location from 5, 10 and 21 d.p.l. mouse brains. c, The predicted spatial abundance of microglia as determined using cell2location in lesion-like compartments. d, The proportions of different cell types within lesion-like compartments in the primary lesion and distal WM, as shown in c. e, Unsupervised clustering of the lesion-like compartments in c. f, The proportions of different clusters from the primary lesion and distal WM in e. g, The expression level and the percentage of pixels from clusters LC1–5 for ADT protein data in spatial ARP-seq. h, Cell types and subclusters of microglia (MC1–3) in e. i, Spatial module scores of disease-associated, foamy and interferon microglial states based on RNA and ATAC data at 5, 10 and 21 d.p.l. in lesion-like compartments. Gene sets were based on a previous study⁷⁵. j, The differential gene expression and GAS for the MC1 (left, red) and MC3 (right, green) microglial subclusters. k, GO analysis of microglial subclusters (MC1, left; MC3, right). Statistical analysis was performed using one-sided Fisher’s exact tests with Benjamini–Hochberg adjustment for multiple comparisons. l, Communication networks of MC1 (top) and MC3 (bottom) microglia with other microglial subtypes and brain cell types, based on CellChat analysis. m, Representative spatial maps of ligand–receptor interaction strength for Fn1–Itga4 (IP-A), Cntn2–Cntnap2 (IP-B), Apoe–Lrp1 (IP-C) and Tgfb3–Tgfbr2 (IP-D), showing regional enrichment within lesion-like compartments at 10 d.p.l. CHOR, choroid plexus; Endo, endothelial cells, BAM, border-associated macrophages.