Fig. 2
DEG analyses of snRNAseq data indicate shared and distinct pathways regulated in EC and DCN of App KI mice. A Integrated UMAP of single-nucleus transcriptomes for all conditions showing main cell types. B Violin plots showing canonical marker gene expression for each labelled cell type: astrocyte 1 [AST1], astrocyte 2 [AST2], Bergmann glia [BG], ependymal [EP], excitatory neurons [EN], Cajal Retzius [CR], interneuron [IN], microglia [MG], peripheral immune [PI], oligodendrocyte 1 [OLIG1], oligodendrocyte 2 [OLIG2], committed oligodendrocyte precursor cells [COP], oligodendrocyte precursor cells [OPC], vascular endothelial [VE], pericytes [P] and leptomeningeal cells [LEP]. C Venn diagram showing overlap in differentially expressed genes (DEGs) found in glial and vascular cells, regardless of cell type, for following DE tests: APP vs WT in EC, APP vs WT in DCN, and EC vs DCN in WT mice. D UMAPs for glia and vascular cells in EC and DCN separated by genotype. Data are integrated separately for each region. Dotted regions highlight cell types with highest numbers of DEGs as indicated in (E): green: microglia (MG); red: astrocytes (AST); blue: oligodendrocytes (OLIG). E DEGs for each glial subtype in each region. “Up” and “Down” denote upregulated and downregulated DEGs in APP compared to WT, respectively. F Correlogram of APP vs. WT LFCs between regions. Upper-right triangle indicates strength of correlation (R) and lower-left triangle indicates % of shared/total DEGs. Darker blue squares and larger circles correspond to cell types that have more similar App KI pathology between regions. G LFC plots comparing differences in gene expression between genotypes in DCN vs. EC for astrocytes, microglia and oligodendrocyte lineage cell subtypes. DEGs in each region are indicated by colour (red: EC; blue: DCN; purple: EC and DCN; grey: not DE). H Top enriched pathways from KEGG, ReactomeDB and Wikipathways for App KI DCN-specific DEGs combined across all glia and vascular cells (228 genes). I STRING protein–protein interactions among App KI DCN-specific DEGs with the top hub gene Pik3r1 labelled. Node size indicates node degree, node colour indicates cell type(s) and line thickness denotes strength of interaction. J Pik3r1 protein–protein interactions (as in I) labelled and enlarged