Extended Data Fig. 9. Mapping complement and MS susceptibility genes onto the snRNA-seq dataset.

(a) Heatmap showing the expression of genes involved in the classical complement cascade, including complement genes, receptors, and regulators. Z-scores are relative to all cells. Most of these genes map onto immune cell, astrocyte, and vascular cell populations.

(b) For each cell population, the number of complement cascade-related genes with Z-score>1.5 is plotted on the UMAP.

(c) Heatmaps showing the expression of genes involved in the classical complement cascade for the immune cell (left, pink) and astrocyte (right, green) subclusters. Z-scores are relative to immune cells and astrocytes, respectively. C1Q, C3, and CFD (C3 activator) were expressed mainly by MIMS-iron, whereas negative regulators of complement activation (LAIR1, LAIR2, CR1) were expressed mainly by homeostatic microglia and perivascular macrophages. C1 complex (C1Q, C1R, C1S, C1QBP), C3, C4, and CALR were expressed mainly by AIMS, whereas C2 and C6 were expressed by some other reactive astrocytes.

(d) Mapping MS-susceptibility risk genes onto the snRNA-seq dataset: the list of 558 prioritized MS susceptibility genes was obtained from a recent genome-wide association study (GWAS)³³ and mapped onto all three snRNA-seq datasets (the current dataset as well as that of Schirmer et al.¹³ and Jäkel et al.²¹). Low-expressed genes (within the 25th percentile average expression) were excluded. MS susceptibility genes were then assigned to clusters if the z-scored average gene expression was >2. Clusters were classified based on the number of MS susceptibility genes (>80, 50–80, 30–50, 1–30 and <10 genes). Results were colour-mapped onto each snRNA-seq UMAP. Most MS susceptibility genes mapped onto the immune and vascular cell clusters. Interestingly, an excitatory neuronal population (“py”) expressed some MS susceptibility genes as well.