Abstract: FR-PO0676
Transcriptomic Analysis of Pkd1 Mutant Mice Reveals Novel Pathways of Dysfunction During Early Cystogenesis
Session Information
- Cystic Kidney Diseases: Basic and Translational Research
November 07, 2025 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Genetic Diseases of the Kidneys
- 1201 Genetic Diseases of the Kidneys: Monogenic Kidney Diseases
Authors
- Marquez, Jonathan, University of Washington, Seattle, Washington, United States
- Houghtaling, Scott Robert, Seattle Children's Hospital, Seattle, Washington, United States
- Gombart, Sean, Seattle Children's Hospital, Seattle, Washington, United States
- Nguyen, Elizabeth D., University of Washington, Seattle, Washington, United States
- Beier, David R., Seattle Children's Hospital, Seattle, Washington, United States
Background
Autosomal dominant polycystic kidney disease (ADPKD) occurs because of genetic variants predominantly affecting PKD1. PKD manifests as progressive cyst formation that impedes surrounding kidney function. Disease progression is highly variable and no existing treatment strategies have been effective in preventing cyst formation. Further, the mechanisms underlying cyst formation remain unclear. Pkd1R3277C/R3277C (RC) mice serve as a model of gradual cystogenesis and provide an opportunity for assessing kidney changes over multiple timepoints. Here, we use this mouse model to develop a transcriptomic atlas of early largely pre-cystic kidney timepoints.
Methods
Single nucleus RNA-sequencing was carried out on whole kidneys from RC and control P10 and P20 B6 mice. Unsupervised clustering, cell type annotation, and gene expression analyses were conducted using Monocle. Pathway analysis was completed using VISION.
Results
We successfully generated a transcriptomic dataset comprised of over 800,000 cells across 2 early timepoints. We were further able to annotate all major kidney cell types within each condition and apply differential gene expression-based pathway analysis to identify novel pathways that appear dysregulated in early cystogenesis within cells of the distal convoluted tubule.
Conclusion
Our work builds upon recent advances in transcriptomic analysis of cystic kidney tissue and assessed early pre-cystic time points to aid in identifying pathways leading to cyst formation and potential therapeutic targets for disease treatment and prevention.