Fig. 2
Trem2R47H NSS induces increased inflammatory response but reduces myelination gene expression in response to cuprizone. a Volcano plot of differentially expressed genes (DEG), displaying fold change of genes (log2 scale) and P values (− log10 scale) between cuprizone (CPZ) treatment vs. control across 4 groups; wild-type, Trem2R47H NSS, Trem2R47H CSS, and Trem2 KO (FC = 0.5, FDR < 0.05). b Heatmap of selected DEG from Trem2R47H NSS (FDR < 0.05 for CPZ vs. control) compared across mouse models (see color scheme in b). Asterisk denotes the group of interest, Trem2R47H NSS on CPZ. c, d List of inflammation DEG upregulated in CPZ compared to control diet that are found to be either (c) Trem2-dependent (upregulated in all groups but Trem2 KO) or (d) Trem2-independent (upregulated in all groups). e List of uniquely downregulated DEG only found in Trem2R47H NSS. f List of myelination-related genes seen down-regulated in CPZ-treated mice across all groups. g Subset of modulerait relationship heatmap by PyWGCNA on wild-type, Trem2R47H NSS, Trem2R47H CSS, and Trem2 KO associated with CPZ treatment. Color corresponding to correlation (red denotes positive correlation; blue denotes negative correlation) and the number in parenthesis shows relative significance of each correlation. Two modules (white and lightcoral modules) were chosen based on their significant correlation with CPZ treatment. h, j Barplots for the eigengene of the genes in the white and lightcoral modules, respectively. i k Gene ontology analysis of the genes in the white and lightcoral modules, respectively. n = 4–8. Data are represented as mean ± SEM. Two-way ANOVA followed by Tukey’s post hoc tests to examine biologically relevant interactions. Statistical significance is denoted by *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001