Extended Data Fig. 2: Cluster characterization of the myeloid cell subsets in control and ALSP samples.

a. UMAP plots of expression of feature genes in different myeloid clusters (re-cluster from the Micro cluster in Fig. 1a). b. Heatmap showing the average gene expression of the top upregulated microglia genes in ALSP versus healthy control samples. c. Box plots showing average individual expression levels for selected DEGs in the myeloid cell cluster. P values were calculated by two-sided Wilcoxon rank-sum test (n = 13 controls; n = 6 ALSP). d. UMAP plot of gene module score of genes related to ferroptosis pathway (Wikipathway: WP4313) (left panel); Violin plot of FTL expression in myeloid cells between the conditions (right panel). P values were determined by two-sided Wilcoxon rank-sum test. e. UMAP plots of control and ALSP brain myeloid cells grouped by different brain regions. For the brain regions, frontal cortex (FC), occipital cortex (OC), subcortical regions (SC), parietal and temporal lobes, basal ganglia (BG), and white matter (WM) were analyzed. f-h. Violin plots displaying the gene set scores of DEGs derived from two AD datasets (f), two MS datasets (g), and LDAM dataset (h) in control and ALSP myeloid cells. The gene set scores were calculated by UCell. P values were determined by two-sided Wilcoxon rank-sum test. Box center lines, bounds of boxes and whiskers indicate median, first and third quartiles and minima and maxima within a 1.5× IQR, respectively. i. Representative images of Oil Red O, CD163 and Hematoxylin staining in the white matter of control and ALSP brain samples. j-k. Scatter plot showing linear regression of average expression levels between CSF1R and selected genes, revealing they are positively (j) or negatively (k) correlated with CSF1R. Gray shading represents the 95% confidence interval; Pearson’s correlation coefficient and P value are shown.