Abstract: SA-PO0035
Study on the Mechanism of Podocyte Progenitors Injury in Alport Syndrome Driven by the COL4A3 G997E Variant
Session Information
- Development, Stem Cells, and Regenerative Medicine
October 24, 2026 | Location: Exhibit Hall A, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Development, Stem Cells, and Regenerative Medicine
- 700 Development, Stem Cells, and Regenerative Medicine
Authors
- Zhao, Ziyi, Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Dai, Xuantong, Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Jiang, Gengru, Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Lin, Fujun, Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
Background
Alport syndrome (AS) is the most common inherited glomerular disease. Although podocyte injury has been established as the key disease pathogenesis, whether abnormalities occurred during podocyte development lead to the manifestation of disease remain largely unknown. In the preliminary study of this study, we found that COL4A3-G997E (c.2990G>A) variant was a common pathogenic variant among early-onset Chinese ADAS patients. This study aimed to investigate early molecular alterations associated with this mutation.
Methods
Urine-derived podocytes from three patients and controls underwent RNA-seq. We then generated iPSCs with homozygous COL4A3-G997E knock-in. Wild-type and mutant iPSCs were differentiated into kidney organoids, followed by scRNA-seq at day 15 of differentiation.
Results
Patient podocytes showed reduced SLC7A11 and increased GPX1/4 expression (Figure 1). Organoid scRNA-seq identified 433 downregulated and 134 upregulated genes in mutant precursors. SLC7A11 was markedly suppressed. KEGG analysis revealed heightened ferroptosis susceptibility before terminal differentiation (Figure 2).
Conclusion
COL4A3-G997E impairs podocyte precursors by suppressing SLC7A11 and activating ferroptosis. This developmental vulnerability highlights a potential early therapeutic target in AS.
Funding
- Government Support – Non-U.S.