Fig. 4

TPPU treatment suppresses DAM and IFN microglia clusters. (A) UMAP representation of snRNA-seq data showing 5,169 microglial cells from the hippocampi of WT_Veh, WT_TPPU, PS19_Veh and PS19_TPPU mice. HM: homeostatic microglia; DAM: disease-associated microglia; IFN: interferon-responsive microglia. (B) UMAP representation of snRNA-seq in WT_Veh, WT_TPPU, PS19_Veh and PS19_TPPU groups. (C) Stacked barplot showing compositions of microglial subclusters across different groups. The bars are colored by their corresponding cell classes as labeled in (A). (D) Close-up of the UMAP embedding of microglial subtypes. Arrows indicate overlaid RNA velocity streamlines showing the cell-state transitions inferred by scVelo’s dynamical mode from the displayed cells. (E) Volcano plot showing the differentially expressed genes in microglia of PS19_Veh relative to WT_Veh mice. Upregulated genes are highlighted in red color. Downregulated genes are highlighted in blue color. (F) KEGG pathway enrichment for the upregulated genes in microglial cells of PS19_Veh relative to WT_Veh. The enriched pathways are highlighted in red color. (G) Volcano plot showing the differentially expressed genes in microglial cells of PS19_TPPU relative to PS19_Veh mice. Upregulated genes are highlighted in red color. Downregulated genes are highlighted in blue color. (H) KEGG pathway enrichment for downregulated genes in microglia of PS19_TPPU relative to PS19_Veh. The enriched pathways for downregulated genes are highlighted in blue color. See also Figure S6