Abstract: SA-PO0028
Integrated Single-Cell Analysis and In Silico Modeling Suggest Birth-Associated Adaptive Actin Remodeling in Kidney Tubules
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
- Park, Jubin B., Vanderbilt University Medical Center, Nashville, Tennessee, United States
- Bayazid, Al Borhan, Vanderbilt University Medical Center, Nashville, Tennessee, United States
- Zhang, Richard R., Vanderbilt University Medical Center, Nashville, Tennessee, United States
- Viquez, Olga, Vanderbilt University Medical Center, Nashville, Tennessee, United States
- Dong, Xinyu, Vanderbilt University Medical Center, Nashville, Tennessee, United States
- Jannotta, Ryan Michael, Vanderbilt University Medical Center, Nashville, Tennessee, United States
- Pozzi, Ambra, Vanderbilt University Medical Center, Nashville, Tennessee, United States
- Zent, Roy, Vanderbilt University Medical Center, Nashville, Tennessee, United States
- Bock, Fabian, Vanderbilt University Medical Center, Nashville, Tennessee, United States
Background
At birth, the kidney rapidly transitions to extrauterine life, when filtration, tubular fluid flow, and luminal pressure rise sharply. This creates a mechanical challenge for developing tubular epithelial cells and coincides with the period when many congenital tubular and cystic kidney diseases worsen. The actin cytoskeleton helps epithelial cells maintain shape and resist mechanical stress, but how this system matures around birth is not well understood.
Methods
We analyzed two public mouse single-cell kidney datasets spanning late fetal and early postnatal development. Curated actin-related transcript programs were scored across nephron tubular epithelial populations to assess birth-associated changes in actin turnover, contractility, cross-linking/bundling, branching, and monomer-binding. Key transcriptomic findings were validated by confocal microscopy. To ask whether these changes could affect tubular shape, we used simplified computer models of a pressurized epithelial tubule and cyst-like lumen expansion.
Results
Across both datasets, tubular epithelial cells showed a consistent shift in actin programs after birth. Late fetal tubules showed features of a more flexible, remodeling actin state, whereas postnatal tubules shifted toward actin programs expected to strengthen and stabilize the epithelial cortex, including increased filament bundling and cross-linking and reduced actin monomer binding. Confocal imaging supported these transcriptomic predictions at the protein level. In mechanical simulations, a fetal-like, mechanically immature epithelium was more easily deformed by luminal pressure, resulting in exaggerated tubular dilation and cyst-like expansion. In contrast, increasing epithelial stiffness, as predicted from increased cross-linking and contractility, limited lumen enlargement and reduced cyst-like deformation.
Conclusion
These data suggest that birth is accompanied by a coordinated maturation of the tubular epithelial actin cytoskeleton from a flexible fetal state toward a mechanically reinforced postnatal state. This transition may help developing nephrons withstand the sudden rise in filtration, flow, and luminal pressure. Conversely, failure to complete this cytoskeletal reinforcement program could make tubules more vulnerable to dilation and cystic remodeling.
Acknowledgment
NIH-NIDDK K08DK134879 (F.B.)
Funding
- NIDDK Support