Fig. 5: Substantia nigra astrocytes in PD upregulate neuroinflammatory pathways.

UMAP plots of cingulate cortex astrocytes grouped by condition (a) and lineage/subtype (b). c Dot plot of select gene (y-axis) marker expression in cingulate astrocytes 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 protoplasmic astrocytes 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 Representative multiplex immunofluorescence showing CD44 (red), GFAP (green), and DAPI+ nuclei in the SN from a control and a PD donor. Scale bar: 20 µm. i Quantification of the CD44+ astrocytes as a proportion of all SN GFAP+ astrocytes in PD and controls. N = 5 for control and n = 6 for PD. Two-tailed Mann-Whitney test p-value is 0.0043. Data is shown as mean +/- SEM. j Dot plot showing KEGG pathway enrichment scores and adjusted two-sided p-values of select pathways of protoplasmic astrocytes in the SN and cingulate cortex. The size of each dot represents its fold enrichment value, and the color represents its –log10 p-value, with yellow denoting lower significance and red indicating higher significance. Only statistically significant terms are shown. k Preranked gene set enrichment analysis of JAK/STAT KEGG pathway in PD protoplasmic astrocyte genes ranked by their fold change from control. Normalized enrichment scores and adjusted two-sided p-values are indicated.