Fig. 4

Microglia subpopulations found in human substantia nigra pars compacta and their response to PD. A Re-clustering of microglia identified in Fig. 1B. B Proportion of nuclei coming from Control (blue) and PD (red) patients per subpopulation reported in Fig. 4A. Different shades of blue and red represent different donors. C A comparison of nuclei number (expressed as a percentage) deriving from PD or Control brains against their predicted abundance (based on 50.19% of all nuclei originating from PD samples: dashed line). A Binomial test was performed to see if there is any significant divergence of cell proportions from this value, * p-value < 0.05, ** p-value < 0.0005, *** p-value < 0.00005. D Selected marker genes for microglial populations shown in Fig. 4A. The full list of marker genes is reported in Supplementary Table 5. E A summary of pathway over-representation analysis using the marker genes defining microglia populations 0–5. Two Sankey diagrams are shown which illustrate the relationships between the various microglia subpopulations and relevant cellular pathways identified (listed in Supplementary Table 6 in the column labeled “Group”). The thickness of the grey interconnecting lines is proportional to the number of individual pathways falling within a particular functional group that is significantly over-represented among the markers of a given cellular subpopulation, normalized to the number of pathways displayed per Sankey plot. F A stripe chart reporting the number of significantly up- or downregulated genes in nuclei originating from PD donors (compared to Controls) per microglial subpopulation, found by fitting a linear mixed model. Red dots correspond to genes that are up- (coefficient > 0) or downregulated (coefficient < 0), with an adjusted p-value < 0.1 (ANOVA test with Benjamini–Hochberg correction). The full list of genes up- or downregulated in the various microglia subpopulations isolated from PD patients is reported in Supplementary Table 7. G Volcano plots reporting genes up- (cyan) or downregulated (orange) in nuclei originating from PD donors (compared to Controls): two microglia populations (Microglia1 and Microglia3) are shown. H Pathways over-represented by up- or downregulated genes in nuclei from PD patients (compared to Controls) and assigned to subpopulations Microglia1 and Microglia3, as reported in Supplementary Table 8