Fig. 3: Single-cell transcriptomic profiling of the db/db mouse model reveals conserved cellular alterations.

a Comprehensive atlas of renal cell types in diabetic and control mice. UMAP visualization of 151,009 high-quality cells obtained from renal tissues of diabetic (db/db, n = 3) and non-diabetic control (db/m, n = 3) mice. Single-cell suspensions were processed using the 10× Genomics platform. Cells are color-coded by their identity across 10 major renal cell types: Renal corpuscle cell, Proximal tubular cell (PT cell), General proximal cell (GPC cell), Loop of Henle cell, Endothelial cell, Proliferative cell, Mononuclear phagocyte (MP cell), Smooth muscle cell, Conventional dendritic cell (CDC cell), and Podocyte. b Quantitative shifts in renal cellular composition. Petal pie chart comparing the proportional abundance of each major cell type expressed as a percentage of total cells. c High-resolution clustering reveals novel cellular subpopulations. UMAP visualization of re-clustered cells within each major cell type states. d Cell-type-specific transcriptional alterations in diabetes mice kidney. Heatmap displaying the top significantly differentially expressed genes (columns) for each major cell type (rows) in db/db compared to db/m mice. Z-scores of normalized expression demonstrate both conserved and cell-type-specific responses to diabetic states. e Genome-wide differential gene expression profile. Volcano plot visualizing all differentially expressed genes in db/db versus db/m mice across all cell types. Significantly upregulated (red) and downregulated (green) genes are highlighted. f Pathway-level consequences of transcriptional alterations in each cell type. Bar graph showing the top 3 significantly enriched KEGG pathways based on genes differentially expressed in db/db kidneys. Critical pathways, including glycerophospholipid metabolism, MAPK signaling pathway, and glutathione metabolism are prominently enriched in podocytes, revealing systemic metabolic dysregulation. g Violin plots showing expression of major cell type identity based on the canonical marker genes used for cell type annotation.