Abstract: TH-PO0543
Mesenchymal Progenitor Cell Maturation in the Early Postnatal Kidneys
Session Information
- Development, Stem Cells, and Regenerative Medicine
November 06, 2025 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Development, Stem Cells, and Regenerative Medicine
- 600 Development, Stem Cells, and Regenerative Medicine
Authors
- Rajadhyaksha, Evan Ajit, Indiana University School of Medicine, Indianapolis, Indiana, United States
- Yennapureddy, Soumya, Indiana University School of Medicine, Indianapolis, Indiana, United States
- Melo Ferreira, Ricardo, Indiana University School of Medicine, Indianapolis, Indiana, United States
- Knoten, Amanda, Washington University in St Louis, St. Louis, Missouri, United States
- Trachtova, Katerina, Washington University in St Louis, St. Louis, Missouri, United States
- Halabi, Carmen M., Washington University in St Louis, St. Louis, Missouri, United States
- Pryhuber, Gloria S, University of Rochester School of Medicine and Dentistry, Rochester, New York, United States
- Jain, Sanjay, Washington University in St Louis, St. Louis, Missouri, United States
- Eadon, Michael T., Indiana University School of Medicine, Indianapolis, Indiana, United States
Background
The developmental processes of the postnatal kidney are complex but may hold insights into understanding injury repair processes. We sought to spatially localize neonatal progenitor cell types using single-cell Visium HD spatial transcriptomics (ST).
Methods
We integrated ST data from postnatal (3 day old), infant (1 month old), and adult kidneys and used Bin2cell mapping to segment cells based on histology and assign ST reads. Unbiased clusters were manually annotated. Age-related changes were evaluated through differential expression analysis.
Results
Unbiased clustering revealed 21 cell types. Two progenitor clusters, 13 and 18, were enriched within the neonatal sample (Figure 1A-B). Cluster 13 localized to the cortex & expressed markers of epithelial cell growth and repair (PROM1, PAX8, VCAM1) and ECM remodeling (ADAMTS1, MMP7). Cluster 13 co-clustered with canonical proximal tubule (PT) cells (expressing AQP1, CUBN, and SLC22A6) from the infant and adult samples. There were few adult cluster 13 cells, and those present expressed injury signatures. In contrast, cluster 18 possessed a mixed epithelial (AQP1, AQP2, UMOD), endothelial (ELN), vascular smooth muscle (PDGFRA, TAGLN), and stromal (FN1, SPARC, COL1A1, COL3A1, COL6A3, ACTA2) signature, consistent with a mesenchymal progenitor cell. The neonatal cells were diffusely present in the cortex and medulla. Corresponding cells in the infant and adult samples demonstrated colocalization with expression of CD163, a macrophage cell surface marker (Figure 1C). The transcription factor SOX4, a master regulator of epithelial-mesenchymal transition (EMT), was expressed in both clusters of interest and further upregulated in the neonate compared to the infant and adult samples.
Conclusion
We identified two SOX4+ clusters of mesenchymal origin in neonates that co-clustered with distinct populations of PT or myofibroblasts in infants and adults, with an adaptive PT phenotype in adults. These clusters infer a developmental framework to understand the antiparallel processes of EMT and mesenchymal-to-epithelial maturation.
Funding
- NIDDK Support