Abstract: SA-PO0663
Modeling Sickle Cell Trait-Associated Nephropathies: Genomic and Transcriptomic Insights from Unaffected Patient-Derived Kidney Samples
Session Information
- Pediatric Nephrology: Transplantation, Hypertension, AKI, Genetics, and Developmental Diseases
November 08, 2025 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Pediatric Nephrology
- 1900 Pediatric Nephrology
Authors
- Williams, Adaysha C., Emory University School of Medicine, Department of Pediatrics, Atlanta, Georgia, United States
- Skinner, Katie, Emory University Laney Graduate School, Atlanta, Georgia, United States
- Wood, Rebeccah G, Emory University School of Medicine, Department of Pediatrics, Atlanta, Georgia, United States
- Archer, David, Emory University School of Medicine, Department of Pediatrics, Atlanta, Georgia, United States
- Sheehan, Vivien, Emory University School of Medicine, Department of Pediatrics, Atlanta, Georgia, United States
- Hong, Andrew L, Emory University School of Medicine, Department of Pediatrics, Atlanta, Georgia, United States
Background
Sickle cell trait (SCT), caused by a heterozygous mutation in the β-globin (HBB) gene, is linked to renal pathologies like chronic kidney disease (CKD) and renal medullary carcinoma (RMC). However, the lack of accessibility of renal tissue from individuals with SCT which limits our understanding of SCT-related nephropathies. We hypothesize that using healthy, non-cancerous kidney tissue from patients with RMC will give us an opportunity to work with SCT samples while identifying the microenvironmental and genetic factors that precede renal disease development.
Methods
To validate our healthy, non-cancerous samples, we performed whole genome sequencing to confirm the HBB mutation (T→A) and used bulk-RNA sequencing to examine gene expression changes within the kidney tissue versus patient-derived non-cancer cell lines.
Results
We confirmed the presence of the missense mutation in HBB leading to Glu6Val and observed conserved single nucleotide variants (SNVs) common in renal-related genes (e.g. PODX, FLT1). Differential gene expressed analyses revealed an upregulation of pathways in the tissue indicative of cell-of-origin heterogeneity with enrichment of cytokines (IL-1β/10/18, IFNγ) and markers of fibrosis (CD248, PDGFRα/β) as compared to the patient-derived cell lines.
Conclusion
Preliminary results suggest that the patient-derived cell lines are genomically similar to their matched tissue samples but differ transcriptionally. While cell lines may allow for interrogation of SCT nephropathies in a simpler manner, we acknowledge their inherent limitations (i.e. short-term propagation). We plan to use functional genomics to develop in vitro models which better recapitulate what is seen in renal SCT tissues. In parallel, through utilization of humanized murine model of sickle cell trait (Townes mouse), additional renal physiological measurements will be performed to aid in identifying SCT-specific factors that precede CKD or RMC development.
Funding
- NIDDK Support