Abstract: SA-PO0025
Comparative Transcriptomic Framework Across Kidney Organoid, Assembloid, and Transplantation Models
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
- Glibetic, Natalija, University of Hawai'i at Manoa, Honolulu, Hawaii, United States
- Barnhill, Jason, University of Hawai'i at Manoa, Honolulu, Hawaii, United States
- Ortega, Michael, University of Hawai'i at Manoa, Honolulu, Hawaii, United States
Background
Human kidney organoids recapitulate key aspects of renal development and have emerged as valuable platforms for disease modeling, nephrotoxicity screening, and therapeutic development. However, the diversity of available protocols with distinct compositions, developmental stages, and functional capabilities has made systematic comparison and evidence-based model selection challenging.
Methods
We collected sc/snRNA-seq datasets from 11 organoid, assembloid, and transplantation protocols and performed two-stage integration and annotation. All datasets were first integrated with fetal kidney references (weeks 9-18; 192,515 cells) using Harmony-based batch correction and annotated using DevKidCC (DKCC). DKCC-annotated cells were then integrated with healthy mature kidney tissue (KPMP v.15, ages 30-50; 194,414 cells), generating a unified annotation spanning developmental and adult kidney identity. Cells were subset into four segments: renal corpuscle, proximal nephron, distal nephron, and ureteric epithelium. Transcriptional positioning was quantified using pseudobulk z-scored expression of curated mature kidney marker gene sets. Mechanotransduction pathway activity was assessed using literature-based curated gene sets for YAP/Hippo, cilia-AMPK, and integrin-focal adhesion signaling.
Results
Protocol advantages in transcriptional progression toward adult states are segment-specific rather than global. Assembloid protocols show the most advanced podocyte and epithelial signatures, transplantation drives metabolic activation in tubular compartments, and no protocol achieves functionally adult-like proximal tubule identity. Convergent mechanosensing pathway activation is shared between assembloid and transplantation models independently of vascularization, possibly implicating physical culture environment as an underappreciated driver of nephron developmental progression.
Conclusion
Together, these findings provide a principled, application-driven framework for kidney organoid model selection, with physical culture environment as an underappreciated and potentially targetable driver of nephron developmental progression. This benchmarking strategy is broadly applicable to organoid systems beyond the kidney.
Acknowledgment
This study was funded by NIH NIDDK R21DK133754 and NIGMS P20GM113134 to M.O. and P20GM103466 to J.B.
Funding
- NIDDK Support