SnRNA-seq Identifies Cell-Specific Pathways in IgAN

In a poster presentation at ASN Kidney Week 2024 titled Single-Nucleus RNA Sequencing (SnRNA-seq) of Biopsy-Confirmed IgA Nephropathy Reveals Cell-Specific Transcriptomic Alteration, Jeongmin Cho and colleagues shared results of single-nucleus RNA sequencing (SnRNA-seq) data from biopsy-confirmed IgA nephropathy (IgAN) cases.

The researchers’ goal was to investigate and identify cell-specific alterations in the transcriptome. SnRNA-seq is known as a reliable way of identifying cell-specific transcriptomic alterations in kidney cells.

Researchers utilized snap-frozen kidney biopsy tissues from six cases of IgAN and seven nephrectomy control cases. The latter group included three cases of diabetic kidney disease, six cases of minimal change disease, and six cases of phospholipase A2 receptor antibody positive membranous nephropathy.

The team performed SnRNA-seq on the kidney tissues and used uniform manifold approximation and projection clustering to identify kidney cells. They examined differences in the proportion of kidney cell types, identified differentially expressed genes (DEGs), and sought representative gene loci previously reported in a multiethnic, genome-wide association study (GWAS).

The transcriptomic profiles of >50,000 cells from IgAN were identified, with substantial enrichment of intraglomerular cells. DEG analysis found that, compared to the nephrectomy and disease control cases, there were a high number of DEGs in mesangial cells, fibroblasts, and vascular smooth muscle cells in the IgAN transcriptome. Gene set enrichment analysis found that the epithelial-mesenchymal transition pathway was enriched in the glomerular cells of IgAN. Consistent across control groups, ETS1 was the most significantly highly expressed gene among the GWAS loci in the mesangial cells of IgAN.

This study, the largest SnRNA-Seq profiling of IgAN kidney cells to date, identified noteworthy cell-specific pathways in IgAN. Given its significance in the previous GWAS and current SnRNA-seq data, ETS1 may be a causal factor within the kidney for IgAN pathophysiology.

Source: Cho J, Park S, Koh JH, Kim Y, DK Kim. Single-nucleus RNA sequencing (SnRNA-seq) of biopsy-confirmed IgA nephropathy reveals cell-specific transcriptomic alteration. TH-PO539. Abstract of a poster presented at the American Society of Nephrology Kidney Week 2024; October 24, 2024; San Diego, California.