Abstract: FR-PO0921
Spatiotemporally Resolved Gene Regulatory Networks Drive Postnatal Human Kidney Maturation
Session Information
- Pediatric Nephrology: Genetic Diseases, Development, Neonatal Nephrology, Glomerular Diseases, and More
October 23, 2026 | Location: Exhibit Hall A, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Pediatric Nephrology
- 1800 Pediatric Nephrology
Authors
- Trachtova, Katerina, Washington University in St Louis, St. Louis, Missouri, United States
- Cheng, Tao, Washington University in St Louis, St. Louis, Missouri, United States
- Yennapureddy, Soumya, Indiana University, Bloomington, Indiana, United States
- Reinert, Stephanie, Washington University in St Louis, St. Louis, Missouri, United States
- Melo Ferreira, Ricardo, Indiana University, Bloomington, Indiana, United States
- Rajadhyaksha, Evan Ajit, Indiana University, Bloomington, Indiana, United States
- Zhang, Bo, Washington University in St Louis, St. Louis, Missouri, United States
- Knoten, Amanda, Washington University in St Louis, St. Louis, Missouri, United States
- Huyck, Heidie L., University of Rochester, Rochester, New York, United States
- Purkerson, Jeffrey M., University of Rochester, Rochester, New York, United States
- Kaushal, Madhurima, Washington University in St Louis, St. Louis, Missouri, United States
- Gaut, Joseph, Washington University in St Louis, St. Louis, Missouri, United States
- Pryhuber, Gloria S., University of Rochester, Rochester, New York, United States
- Eadon, Michael T., Indiana University, Bloomington, Indiana, United States
- Jain, Sanjay, Washington University in St Louis, St. Louis, Missouri, United States
Group or Team Name
- Pediatric Center of Excellence in Nephrology at WashU
Background
Identifying the spatiotemporal molecular dynamics of postnatal human kidney development is integral to understanding pediatric kidney disease and the engineering of healthy replacements. Despite our rich understanding of embryonic and adult kidneys, there is a knowledge gap in the cell dynamics of the early postnatal kidney. Overcoming tissue availability challenges, we built an infrastructure to decipher regulatory programs using same cell multimodal snRNA and ATAC seq data and high-quality spatially resolved transcriptomic data from pediatric kidneys.
Methods
We applied Xenium Prime 5k+100 targeted spatial transcriptomics to 10 samples (10 participants) and Visium HD genome-wide spatial transcriptomics to 18 samples (10 participants) ranging from newborn to adolescent healthy and diseased donor kidneys. We developed a pipeline to integrate data across ages for the analysis of 2.5 million Xenium and 4 million Visium HD cells. Cells were annotated using our concurrently generated pediatric multimodal atlas of 141k nuclei (25 samples).
Results
Integrated analyses of all datasets revealed several novel insights. We identified two unique neonatal populations with distinct locations in the outer Bowmans capsule that are potential progenitors for podocytes and/or proximal tubules/PECs. There was distinct zonation of these cells from outer to inner cortex and regulation by expression of discreet transcription factors such as the FOX family that evolved with age. Several nephron segments, fibroblasts and immune cells also showed dynamic changes with tissue depth across age span, forming unique niches along the tubules. Notably, we identified a neonatal-specific fibroblast enriched in neural guidance pathways, suggesting early neurotropic roles. Fibroblast populations further participate in regulatory programs driving tubule maturation including retinoic acid, FGF, and WNT signaling pathways.
Conclusion
We decode a spatiotemporal map of early postnatal human kidney as a benchmark to understand spatial dynamics of kidney maturation and disease, providing insights into the plasticity of cells and their neighborhoods to adapt to neonatal metabolic demands.
Acknowledgment
Funding by NIH NIDDK grant P50DK133943.
We thank WashU PCEN team members Michael Rauchman, Jeannine Basta, Carmen Halabi, Humza Hemani, and the Kidney Translational Reserach Center for support.
Funding
- NIDDK Support