Single-cell RNA-seq with spatial transcriptomics to create an atlas of human diabetic kidney disease.

Diabetic kidney disease (DKD) develops in ~40% of patients with diabetes and is the leading cause of chronic kidney disease worldwide. We used single-cell RNA-sequencing and spatial transcriptomic analyses of kidney specimens from patients with DKD. Unsupervised clustering revealed distinct cell clusters, including epithelial cells and fibroblasts. We also identified differentially expressed genes (DEGs) and assessed enrichment, and cell-cell interactions. Specific enrichment of DKD was evident in venous endothelial cells (VECs) and fibroblasts with elevated CCL19 expression. The DEGs in most kidney parenchymal cells in DKD were primarily enriched in inflammatory signaling pathways. Intercellular crosstalk revealed that most cell interactions in DKD are associated with chemokines. Spatial transcriptomics revealed that VECs co-localized with fibroblasts, with most immune cells being enriched in areas of renal fibrosis. These results provided insight into the cell populations, intercellular interactions, and signaling pathways underlying the pathogenesis and potential targets for treating DKD.