Fig. 7

Unbiased transcriptomic analysis of TG-Abi3-Gngt2^−/− mice reveal distinctive disease-associated gene expression signatures and co-expression modules. a–c Volcano plot (a), list of top 5 upregulated and top 5 downregulated genes (based on fold change; orange, upregulated genes, blue, downregulated genes) (b) and GO pathways based on enriched genes for upregulated genes (c) in 3-month-old APP TG mice with WT (+ / +), or KO (−/−) of Abi3-Gngt2 locus. Orange dots, upregulated genes; blue dots, downregulated genes. FC, fold change; DEG, differentially expressed genes; padj, p-values adjusted for multiple comparison. d Cell type population analyses indicating changes in microglia, astrocytes, neurons, and oligodendrocyte populations in 3-month-old APP TG mice with WT (+ / +), heterozygous (+ /−), or KO (−/−) of Abi3-Gngt2 locus. One-way ANOVA; **p < 0.01, *p < 0.05. e Gene expression signatures for specific microglia or astrocyte subtypes in 3-month-old APP TG mice with WT (+ / +), heterozygous (+ /−), or KO (−/.−) of Abi3-Gngt2 locus. One-way ANOVA; *p < 0.05. f WGCNA gene co-expression modules correlating with experimental traits (biochemical Aβ values, plaque burden, Iba-1 burden, GFAP burden, Abi3-Gngt2 genotype). Correlation of modules to different experimental traits is colored in a heatmap (red, positive correlation; blue, negative correlation). Modules with p-values < 0.05 and correlation value < -0.5 0r >0.5 are indicated in colored tile (see scale on right). Cell-type-specific gene lists were used to identify genes with significant overlap (odds ratio) within the modules. The heatmap is colored by the value of the odds ratio; higher the odds ratio of association, warmer the color. Grey squares indicate non-significant (p  > 0.05, odds ratio < 2) overlaps in the gene lists. N = 4 mice (2 males, 2 females) per Abi3-Gngt2 genotype except 1 outlier removed in d, e. All p-values adjusted for multiple comparisons (padj)