Fig. 4

Unbiased transcriptomic analysis of Abi3-Gngt2^−/− mice reveal upregulation of immune pathways and disease-related gene expression patterns. 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 (c) in 3-month-old Abi3-Gngt2^−/− mice relative to Abi3-Gngt2^+/+ mice. Orange dots, upregulated genes; blue dots, downregulated genes (a). 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 mice with WT (+ / +), heterozygous (+ /−), or KO (−/−) of Abi3-Gngt2 locus. One-way ANOVA, ***p < 0.001, **p < 0.01, *p < 0.05. e Gene expression signatures for microglia or astrocyte functional subtypes in 3-month-old mice with WT (+ / +), heterozygous (+ /−), or KO (−/−) of Abi3-Gngt2 locus. These cell-type-specific signatures were identified in previous studies [21,22,23,24,25,26,27,28]. One-way ANOVA, **p < 0.01. f WGCNA gene co-expression modules correlating with specific experimental traits (Iba-1 burden, GFAP burden, and Abi3-Gngt2^−/− genotype) shown. 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 or > 0.5 are indicated in colored tiles (see scale on right). Cell-type-specific gene lists were used to identify genes with significant overlap (odds ratio, see scale on right) 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. All p-values adjusted for multiple comparisons (padj). n = 4 mice (2 males, 2 females) per Abi3-Gngt2 genotype except 1 outlier removed in d, e