Abstract: TH-OR030
Pediatric Multiomic and Spatial Kidney Atlas Identifies Regulatory Networks Driving Postnatal Kidney Maturation
Session Information
- Genetics of Complex Kidney Traits
November 06, 2025 | Location: Room 360A, Convention Center
Abstract Time: 04:50 PM - 05:00 PM
Category: Pediatric Nephrology
- 1900 Pediatric Nephrology
Authors
- Trachtova, Katerina, Washington University in St Louis School of Medicine, St. Louis, Missouri, United States
- Zhang, Bo, Washington University in St Louis School of Medicine, St. Louis, Missouri, United States
- Melo Ferreira, Ricardo, Indiana University School of Medicine, Indianapolis, Indiana, United States
- Cheng, Tao, Washington University in St Louis School of Medicine, St. Louis, Missouri, United States
- Rajadhyaksha, Evan Ajit, Indiana University School of Medicine, Indianapolis, Indiana, United States
- Knoten, Amanda, Washington University in St Louis School of Medicine, St. Louis, Missouri, United States
- Huyck, Heidie L., University of Rochester Medical Center, Rochester, New York, United States
- Purkerson, Jeffrey M., University of Rochester Medical Center, Rochester, New York, United States
- Kaushal, Madhurima, Washington University in St Louis School of Medicine, St. Louis, Missouri, United States
- Gaut, Joseph, Washington University in St Louis School of Medicine, St. Louis, Missouri, United States
- Eadon, Michael T., Indiana University School of Medicine, Indianapolis, Indiana, United States
- Pryhuber, Gloria S, University of Rochester Medical Center, Rochester, New York, United States
- Jain, Sanjay, Washington University in St Louis School of Medicine, St. Louis, Missouri, United States
Group or Team Name
- Pediatric Center of Excellence in Nephrology at WashU.
Background
Despite its completion of nephrogenesis prior to term birth, the human kidney must mature along the pediatric lifespan to successfully regulate homeostasis. The underlying cellular mechanisms and regulations of maturation are largely unknown. Such knowledge is critical to understanding congenital and acquired pediatric kidney disease and the engineering of healthy tissue. The lack of a benchmark reference atlas is due in part to the difficulty of acquiring high quality pediatric kidney tissue. We bridge these gaps using the WashU PCEN to present the first comprehensive single cell and spatial human pediatric kidney atlas and reveal regulatory networks driving glomerular maturation.
Methods
We applied 10x multiome (snRNA-ATAC-seq) and Visium/HD spatial transcriptomics to 27 pediatric kidney tissue samples (20 participants) ranging from newborn to adolescence from healthy and diseased donor kidneys procured by extensive infrastructure for pediatric tissue collection. We developed a computational pipeline to integrate data across all ages with annotations and spatial validations for trajectory and regulatory analysis.
Results
Analysis of 17 reference and 10 disease samples provided 157k post-QC nuclei with 136k having dual snRNA and ATAC data. We detected all kidney lineages including rare cell types across the entire nephron, interstitium and vasculature delineating chromatin accessibility and key transcription factors across the pediatric age span. Notably, we deciphered a novel cell cluster of likely precursors of parietal epithelial cells and podocytes enriched in newborns that show a well-defined pseudotime trajectory with associated TFs pointed towards their mature states. Pathways along these transitions include developmental, cilial, neuronal, extra cellular, metabolic and cytoskeletal dynamics, many of which are associated with adult reparative states. Visium/HD validations showed unique organization of the various stages of maturity across the renal corpuscle.
Conclusion
This report represents the first single cell and spatial human pediatric kidney atlas and will be a key benchmark for understanding a variety of pediatric kidney diseases and potential targets to promote healthy recovery.
Funding
- NIDDK Support