Single-nucleus transcriptomic landscape of human glomerular diseases [Xenium]

Disease-specific similarities and differences in single-cell-level transcriptomic alterations in various glomerular diseases are necessary to understand the pathophysiology of kidney glomerular diseases. We analyzed single-nucleus RNA sequencing (snRNA-seq) data from 262,984 nuclei from kidney biopsy cores from 28 subjects with glomerular disease, including minimal change disease, membranous nephropathy, IgA nephropathy, and diabetic kidney disease and control individuals. Our findings revealed that the upregulated differentially expressed genes (DEGs) exhibited disease-specific and cell type-common patterns, and the downregulated DEGs exhibit cell type-specific and disease-common patterns across various cell types. Differences in the transcriptomic profiles of patients with each type of glomerular disease were identified with a distinct pattern of gene expression and the related biological pathways. We also identified specific cell subtypes, including transitional cells between podocytes and parietal epithelial cells, podocytes with endocytosis features, and myofibroblasts, that are associated with the clinical features of glomerular diseases. Overall, we identified transcriptional alterations specific to each cell type or disease subcategory and established a valuable resource for further research on human glomerular disease.