Fig. 4
From: Trem2 deficiency differentially affects phenotype and transcriptome of human APOE3 and APOE4 mice
Lack of Trem2 significantly affects brain transcriptome of mice expressing human APOE3 or APOE4. Gene expression profiling was performed by RNA-seq on tissue from the frontal cortex of the same 6–7 months old mice shown on Fig. 1a. a WGCNA was used to identify correlations between gene expression and four traits: APOE isoform, sex, Trem2 genotype, and human APP transgene. The relationship table shows the correlation between the module eigengene (row) traits (column). Red denotes a positive correlation and blue a negative correlation, with * denoting a significant correlation (* p < 0.05). Trem2 signature module is marked with a red circle. b Bar plots show the aggregated module eigengene for each genotype in the modules of interest. c GO term bar plots indicate the -log10P value for each term. The associated point in the center of each bar represents the percent of submitted genes found in each GO term. d Scatterplot depicts the MM vs GS plot for genes in the lightcyan module relating to the Trem2 genotype, with hub genes defined as MM > 0.8 and GS > 0.2. e The network generated from all connections within the module from the top 5 hub genes (indicated by darker blue color). Characterization of the lightcyan module with fold change bar plots and heatmaps for disease associated microglial genes (DAM) (f), homeostatic (g) microglia genes and genes outside these two categories (others) (h). Heatmaps depict the Z-score for genes downregulated in Trem2ko mice from the lightcyan module. n: E3/Trem2ko = 8; E4/Trem2ko = 8; E3 = 8; E4 = 6; APP/E3/Trem2ko = 14; APP/E4/Trem2ko = 16; APP/E3 = 14; APP/E4 = 14; (equal number males and females). i-j Integration of co-expressed gene network of interest to amyloid deposition. The expression profile of lightcyan was used to identify correlations between gene expression patterns in each of the four APP groups to the percent coverage of 6E10 (i), and percent coverage of X34 (j). Correlation between histological data and RNA-seq data is done with Pearson r correlation