Fig. 5

Distinct microglial responses in PS19-TREM2-WT and PS19-TREM2-R47H mice by scRNA-seq

(A) UMAP plot showing 14 distinct microglial subclusters from PS19-TREM2-WT and PS19-TREM2-R47H mice. n = 6 mice per group (equal male and female). (B) Heatmap displaying the expression of key marker genes used to identify microglial subclusters, including homeostatic microglia (HM1-8), disease-associated microglia (DAM1 and DAM2), interferon response microglia (IRM), MHCII + microglia, ribosomal gene-enriched microglia (REM), and cycling/proliferating microglia (CPM). (C) Bar plots illustrating the proportions of microglial subclusters in each of the four groups. (D and E) Number of DEGs for all the microglia subclusters in the comparison between induced versus Ctrl groups of PS19-TREM2-WT (D) or and PS19-TREM2-R47H (E) mice. (F and G) Top five canonical pathways enriched by DEGs from DAM1 cluster in the comparison between induced versus Ctrl groups of PS19-TREM2-WT (F) or PS19-TREM2-R47H (G) mice. The threshold of significant P value is 0.05. (H) Heatmap showing the gene expression of combined DEGs in the DAM1 cluster from PS19-TREM2-WT and PS19-TREM2-R47H mice. (I) Representative images showing Galectin-3 and IBA1 staining in piriform cortical region. Scale bar is 200 μm and 50 μm for insert. (J and K) The Galectin-3 coverage areas were quantified and compared. n = 19–23 mice/group, each datapoint (circle) represents an individual animal, male and female mice are labeled as solid and open circles, respectively. Data are shown as mean ± SEM. Mann-Whitney tests with Bonferroni correction were used for statistical analysis. P value < 0.05 was considered to be statistically significant. *, P < 0.05; N.S., not significant.