Fig. 6
From: Trem2 deletion enhances tau dispersion and pathology through microglia exosomes
Characterization of proteomic profiles associated with exosome induction in Trem2 KO microglia. A Schematic of the proteomic analysis scheme used; WT or Trem2 KO microglia were left untreated or treated with tau oligomers (run 1) or LPS/ATP (run 2) and microglia lysates were subjected to proteomic analysis by label-free mass spectrometry. B, C PCA plots depicting distribution and clustering of proteomic profiles from WT and Trem2 KO (“KO”) microglia untreated or exposed to tau oligomers (B) or LPS/ATP (C). PCA distribution of 6 individual replicate samples for each treatment group are shown. D Total (left graph) and upregulated (black)/downregulated (gray) (right graph) differentially expressed proteins (DEPs) in microglial cell lysates in four comparative analyses indicated (run 1): Trem2 KO vs WT (both untreated), Trem2 KO vs WT (both +tau), WT – tau vs untreated, and Trem2 KO – tau vs untreated. E Total (left graph) and upregulated (black)/downregulated (gray) (right graph) DEPs in microglial cell lysates in four comparative analyses indicated (run 2): Trem2 KO vs WT (both untreated), Trem2 KO vs WT (both +LPS/ATP), WT – LPS/ATP vs untreated, and Trem2 KO – LPS/ATP vs untreated. F-I Heatmap distribution and scatterplot distribution of overlapping DEPs in WT (x-axis) and Trem2 KO (“KO”) (y-axis) microglia with tau (run 1) and LPS/ATP (run 2) treatment. F Heatmap showing Log2 fold-change and adj p-value of 2867 DEPs in WT and KO microglia with tau treatment; adjacent heatmap depicts z-score values of the genes listed on the left heatmap for individual samples (n = 6) from WT (untreated), Trem2 KO (untreated), WT (+tau) or Trem2 KO (+tau) microglia lysates as indicated; “NA” values derived from missing peptide values are indicated in gray. Log2 fold-change, z-score (red/blue) and p-value (red/yellow) scales are shown. G Scatterplot distribution of 927 overlapping DEPs identified in (F). H Log2 fold-change and adj p-value of 3481 DEPs in WT and KO microglia with LPS/ATP treatment; adjacent heatmap depicts z-score values of the genes listed on the left heatmap for individual samples (n = 6) from WT (untreated), Trem2 KO (untreated), WT (+LPS/ATP) or Trem2 KO (+LPS/ATP) microglia lysates as indicated; “NA” values derived from missing peptide values are indicated in gray. Log2 fold-change, z-score (red/blue) and p-value (red/yellow) scales are shown. I Scatterplot distribution of 1398 overlapping DEPs identified in (H). J Heatmap distribution, Log2 fold-change of GO CC “extracellular exosome” DEPs from combined runs 1 (tau) and 2 (LPS/ATP) from the 8 pairwise comparisons indicated. Z-scores of 6 replicates from each run are shown on the right, “NA” values derived from missing peptide values are indicated in gray