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

Diabetic kidney disease (DKD) develops in similar to 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.

Automated summary

Diabetic kidney disease (DKD), affecting 40% of diabetic patients, is the leading cause of chronic kidney disease worldwide. Through single-cell RNA sequencing and spatial transcriptomic analyses, distinct cell clusters, differentially expressed genes, and cell-cell interactions were identified in kidney specimens from DKD patients. Inflammatory signaling pathways were primarily enriched in most kidney parenchymal cells in DKD. Intercellular crosstalk primarily involved chemokines in DKD. Furthermore, spatial transcriptomics revealed the co-localization of venous endothelial cells and fibroblasts, with immune cells enriched in areas of renal fibrosis. These findings provide valuable insights into DKD pathogenesis and potential therapeutic targets.