Fig. 1

Single-cell RNA sequencing highlights E4-associated changes in glycolysis and oxidative phosphorylation in astrocytes. Whole brain tissue from E3 and E4 mice was digested and subjected to single-cell RNA sequencing (scRNA-seq). a UMAP visualization of cells from E3 and E4 mouse brains (3 pooled hemi-brains per genotype). Cells are colored by cell type. b Assignment of clusters to specific cell types based on expression of known gene markers (astrocytes, Aldoc; microglia, Tmem119; macrophages, Mgl2; oligodendrocytes, Mog; choroid plexus, Kl; ependymal cells, Foxj1; mural cells, Vtn; Ednothelial cells, Emnc; meningeal, Slc47a1; neuroprogenitor cells, Dcx). c, d Expression of both APOE (c) and glycolysis genes (d) was highest in astrocyte cell populations. Glycolysis gene expression is shown as the sum of the expression of 39 detected genes belonging to the KEGG pathway “glycolysis and gluconeogenesis”. e UMAP visualization of astrocytes (Aldoc+ cells). Cells are colored by cluster. f Volcano plot showing differentially expressed genes in E3 and E4 astrocytes. g, h Gene ontology (g) and pathway enrichment (h) analyses highlights APOE-associated gene expression changes in metabolic pathways, particularly mitochondrial complex and oxidative phosphorylation (highlighted in red). Abbreviations: CMV, cytomegalovirus; EC, endocannabinoid; ER, endoplasmic reticulum; GnRH, Gonadotropin-releasing hormone; HV, herpesvirus; KS, Kaposi sarcoma; NAFLD, non-alcoholic fatty liver disease; NT, Neurotrophin; reg., regulation