Fig. 4: Patterns of dysregulation of myeloid cells in the substantia nigra and cingulate cortex.

UMAP plots of cingulate cortex myeloid cells grouped by condition (a) and lineage/subtype (b). c Dot plot of select gene (y-axis) marker expression in cingulate myeloid lineages (x-axis). Size indicates percentage expression, and color indicates normalized expression levels. d same as a but for the substantia nigra (SN). e Same as b but for the SN. f Same as c but for the SN. g Differentially expressed genes (DEGs) of activated microglia in PD vs. control are shown by their log2 fold change (LFC) in the SN on the x-axis and the cingulate on the y-axis. The color indicates if the genes are significantly differentially expressed in the cingulate (Cing), SN, both, or none. DEGs were considered based on two-sided adjusted p-values. h Dot plot showing KEGG pathway enrichment scores and adjusted two-sided p-values of select pathways of activated microglia in the SN and cingulate cortex. The size of each dot represents its fold enrichment value, and the color represents its –log10 two-sided p-value, with yellow denoting lower significance and red indicating higher significance. Only statistically significant terms are shown. i Representative immunohistochemistry showing CD68+ cells (brown chromogen – green arrows) and CD8 + T cells (red chromogen - pink arrows) in the SN from a control and a PD donor. Scale bar: 50 µm. j Quantification of CD68+ cells as a proportion of all SN cells PD and controls. N = 8 for control and n = 6 for PD. Two-tailed Mann-Whitney test p-value is indicated. Data is shown as mean +/- SEM. k Preranked gene set enrichment analysis of previously described PD-murine BAM cluster markers in PD BAM genes ranked by their fold change from control. Normalized enrichment scores and adjusted two-sided p-values are indicated.