Fig. 6

Unbiased transcriptomic analysis of TgCRND8 mice expressing sIl10R and sIl4R. A-C. Volcano plot based on fold change (red, upregulated genes, blue, downregulated genes) with list of top 10 altered genes (A) and GO pathways based on enriched genes (B) in 3-month-old TgCRND8 mice expressing sIl10R relative to control mice. padj, p-values adjusted for multiple comparison; FC, fold change. AD-associated astrocyte or microglia functional subtypes were tabulated in these mice (C). D-E. Volcano plot based on fold change (red, upregulated genes, blue, downregulated genes) with list of top 10 altered genes (D) and GO pathways based on enriched genes (E) in 3-month-old TgCRND8 mice expressing sIl4R relative to control mice. padj, p-values adjusted for multiple comparison; FC, fold change. F. PPI analysis in sIl4R expressing TgCRND8 mice using STRING revealed an enriched network of genes consistent with circadian rhythm function. n = 6mice/group. G. Correlation graph showing significantly changed genes in AAV-sIl10R and sIl4R expressing mice plotted by log2 fold change Genes with congruent changes (grey) are in the upper right (up-regulated) and lower left (down-regulated) quadrants. Unique changes in gene expression (blue) are shown in the upper left quadrant (up-regulated in sIl10R but down-regulated in sIl4R) and the lower right quadrant (down-regulated in sIl10R but up-regulated in sIl4R). Spearman’s correlation analysis was performed and results are indicated. H. GO-seq analysis of the genes that were differentially altered in the sIl10R and sIl4R expressing TgCRND8 mice. I. Differential changes in circadian pathway (Reactome) in sIl10R and sIl4R expressing TgCRND8 mice based on normalized z-score (scale depicted below). DEG, differentially expressed genes; GO, gene ontogeny; Hm, homeostatic; MGnD, neurodegenerative microglia; PPI, protein protein interaction; padj, p-values adjusted for multiple comparisons. n = 6mice/group