Abstract: SA-PO0110
Single-Cell Identification of Disease-Associated Podocyte Population Involved in Early Progression of Alport Syndrome
Session Information
- ADPKD and Cystic Kidney Disease - 3
October 24, 2026 | Location: Exhibit Hall A, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Genetic Diseases of the Kidneys
- 1201 Genetic Diseases of the Kidneys: Cystic (Monogenic)
Authors
- Owaki, Aimi, Kumamoto Daigaku, Kumamoto, Kumamoto Prefecture, Japan
- Kaseda, Shota, Kumamoto Daigaku, Kumamoto, Kumamoto Prefecture, Japan
- Nishinakamura, Ryuichi, Kumamoto Daigaku, Kumamoto, Kumamoto Prefecture, Japan
- Shuto, Tsuyoshi, Kumamoto Daigaku, Kumamoto, Kumamoto Prefecture, Japan
- Suico, Mary Ann, Kumamoto Daigaku, Kumamoto, Kumamoto Prefecture, Japan
- Kai, Hirofumi, Kumamoto Daigaku, Kumamoto, Kumamoto Prefecture, Japan
Background
Alport syndrome (AS) is a progressive hereditary kidney disease caused by abnormalities of the glomerular basement membrane, leading to disruption of the filtration barrier, inflammation, fibrosis, and end-stage kidney disease. Because AS progression is irreversible, early intervention is essential. We previously performed single-cell RNA sequencing (scRNA-seq) in AS mouse model at 5 weeks (pre-disease), and 8 weeks (early disease stage), identifying marked transcriptional changes in podocytes. Among the altered genes, we identified Tnfsf15 as an early-stage disease-protective factor that suppresses proteinuria through glomerular protection (Owaki A et al., J Pharmacol Sci. 2026). However, the podocyte subpopulations involved in AS progression remain unclear.
Methods
Podocytes were extracted from whole-cell scRNA-seq data based on marker gene expression and subjected to subclustering.
Results
We identified a podocyte cluster specifically increased in AS at both 5 and 8 weeks of age. Gene Ontology analysis revealed increased expression of genes related to ECM remodeling associated with kidney fibrosis and glomerulosclerosis, actin filament reorganization, chemotaxis, cell migration, and cell morphogenesis, suggesting that this cluster represents an abnormal podocyte state involved in AS progression. Further analysis of cluster-specific genes revealed high expression of several ligand molecules. To investigate its effects on other glomerular cells, we performed cell-cell communication analysis. This analysis suggested an interaction between cluster 4 podocyte-derived Sema7a and its receptor Itga1 on mesangial cells, which are important for glomerular blood flow regulation and structural maintenance. Sema7a is an immunomodulatory factor involved in T cell-mediated inflammation, but its function in glomerular disease remains unclear. Thus, AS-increased cluster 4 podocytes may affect mesangial cells through Sema7a-Itga1 signaling, contributing to glomerular structural alterations and disease progression.
Conclusion
scRNA-seq analysis identified a podocyte population specifically increased in AS. Future studies will investigate its impact on other glomerular cells and clarify its functional significance in AS progression.