Fig. 10
From: Neuronal transcriptome, tau and synapse loss in Alzheimer’s knock-in mice require prion protein
Prnp-dependence of cell type specific gene expression in DKI mouse model. A The number of AD-associated DEGS in neuronal and glial cell population at 10 (top) and 20-months (bottom) old DKI mice. B Volcano plots of excitatory and inhibitory neurons, and microglia at 10 months. Colored points indicated significant up or downregulated genes in DKI samples as compared to WT. C Venn diagrams showing the number of shared DEGs between excitatory and inhibitory neurons at 10 months, excitatory neurons populations at 10 and 20 months. The statistical significance of gene overlap was assessed by Fisher’s Exact test. D Pie charts illustrating the percentage of DEGs that are fully corrected by PrPC gene deletion (Fisher’s exact test); the size of the chart is relative to total number of DEGs. E Heatmaps showing single DEG expression within each cell type, separated by corrected and non-corrected genes as represented in (D, F). DEG lists showing the remaining cell types are included in Supp. Table S2. F Transcriptome-wide correction by PrPC gene deletion in neuronal and glial cell types. Cell type-specific comparison of AD-associated DEGs and PrPC-corrected DEGs in DKI samples. Log2FC between DKI and WT samples (AD effect) is plotted along the x-axis. Log2FC between DKI and DKI; Prnp−/− samples (PrPC effect) is plotted along the y-axis. Black points represent genes with Log2FC > 0.25 and p < 0.005. Colored points represent DEGs that were corrected by PrPC deletion. Points along the identity line (x = y) represent genes with equivalent differential expression between DKI; Prnp−/− and WT, relative to DKI, indicating complete rescue by PrPC deletion. Points along the line “y = 0” reflect genes unaffected by PrPC. P-values represents the significance of a non-zero linear regression relationship. The regression line (Pearson’s correlations, purple) represents transcriptome-wide effects of PrPC