Abstract: SA-PO0006
Studying Postnatal Nephron Maturation and Disease Using Single-Nucleus Multi-Omics
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
- Hemani, Humza, Washington University in St Louis, St. Louis, Missouri, United States
- Basta, Jeannine M., Washington University in St Louis, St. Louis, Missouri, United States
- Stout, Lisa, Washington University in St Louis, St. Louis, Missouri, United States
- Sosa, Catalina, Washington University in St Louis, St. Louis, Missouri, United States
- Rauchman, Michael I., Washington University in St Louis, St. Louis, Missouri, United States
Group or Team Name
- Rauchman Lab
Background
The kidney undergoes significant physiological and functional maturation after birth, but the molecular mechanisms underpinning these changes and how they link to disease are not well understood. Single-nucleus and spatial methods are well-suited to studying the transcriptional and epigenetic changes occurring in each nephron cell type during maturation to reveal insights into how cellular differentiation and gene regulation are modulated to acquire full renal function.
Methods
Studying Postnatal Nephron Maturation and Disease Using Single-nucleus Multiomics
Results
We identified a cluster of cells expressing both podocyte and parietal epithelial cell (PEC) markers present at post-natal day 1 (P1) and P5, and another cluster present from P1 to P10 expressing proximal tubule (PT) and PEC genes. These clusters appear to be common progenitor clusters for these cell types, which is corroborated by trajectory inference (Slingshot). A cluster of PT cells expressing cell cycling genes was also identified that is most prevalent at P10, as well as a separate cycling thick ascending limb (TAL) population, coinciding with periods of significant growth of the renal tubule. Additionally, we identified separate clusters expressing PT segment 1 (PT-S1) and PT-S2 genes that are prevalent up to week 4 but are nearly absent at later timepoints when the PT is fully mature. These interim clusters do not express cycling genes and play important roles in growth and maturation. Furthermore, in an FSGS model (Mta2 mutants) we identified a cluster of adaptive PT (aPT) cells seen almost exclusively in week 6 and 8 mutants. This cluster of cells exhibits gene expression similar to interim PT clusters, indicating dedifferentiation of PTs occurring during tubular injury.
Conclusion
We have identified putative common progenitor clusters for podocytes, PECs, and PT cells. Additionally, we have identified interim cell states that develop and then disappear during maturation of the PT and TAL. Finally, we found an adaptive PT cluster that develops at later timepoints in an FSGS model that co-expresses injury and immature PT genes.
Prevalence of the cycling PT cluster at each timpeoint. This cluster is most prevalent at P10.
Funding
- NIDDK Support