Abstract: TH-PO539
Single-Nucleus RNA Sequencing (SnRNA-seq) of Biopsy-Confirmed IgA Nephropathy Reveals Cell-Specific Transcriptomic Alteration
Session Information
- Glomerular Diseases: Omics, Biomarkers, and Tools
October 24, 2024 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Glomerular Diseases
- 1401 Glomerular Diseases: Mechanisms, including Podocyte Biology
Authors
- Cho, Jeongmin, Seoul National University College of Medicine, Jongno-gu, Seoul, Korea (the Republic of)
- Park, Sehoon, Seoul National University Hospital, Jongno-gu, Seoul, Korea (the Republic of)
- Koh, Jung Hun, Seoul National University College of Medicine, Jongno-gu, Seoul, Korea (the Republic of)
- Kim, Yaerim, Keimyung University School of Medicine, Daegu, Korea (the Republic of)
- Kim, Dong Ki, Seoul National University Hospital, Jongno-gu, Seoul, Korea (the Republic of)
Background
SnRNA-seq is a valuable method for identifying cell-specific transcriptomic alterations in kidney cells. Our objective was to investigate SnRNA-seq data from biopsy-confirmed IgA nephropathy (IgAN) cases and identify cell-specific alterations in the transcriptome.
Methods
We collected snap-frozen kidney biopsy tissues from 6 cases of IgAN and 7 nephrectomy control cases. The disease control group included 3 cases of diabetic kidney disease, 6 cases of minimal change disease, and 6 PLA2R-Ab positive membranous nephropathy cases. SnRNA-seq was performed on the kidney tissues, and kidney cells were identified through UMAP clustering. We investigated differences in the proportion of kidney cell types and identified differentially expressed genes (DEGs). Additionally, we searched for representative gene loci previously reported in a multiethnic genome-wide association study (GWAS).
Results
We identified transcriptomic profiles of > 50,000 cells from IgAN, with a considerable enrichment of intraglomerular cells. The DEG analysis revealed a high number of DEGs in mesangial cells, fibroblasts, and vascular smooth muscle cells in the IgAN transcriptome compared to the nephrectomy and disease control cases. In the gene set enrichment analysis, the epithelial-mesenchymal transition pathway was enriched in the glomerular cells of IgAN. Among various GWAS loci, ETS1 was the gene significantly highly expressed in the mesangial cells of IgAN, consistent across the compared control groups.
Conclusion
This investigation represents the largest SnRNA-Seq profiling of IgAN kidney cells to date. Notable cell-specific pathways in IgAN were identified. ETS1 may be a kidney-indwelling causal factor for IgAN pathophysiology, considering its significance in both previous GWAS and the current SnRNA-Seq data.