Organoid transplantation in the adult endometrium restores fertility and uncovers epithelial lineage plasticity
- 1University of MIssouri
Abstract
The adult endometrium regenerates repeatedly, yet the cells and mechanisms that rebuild its epithelium remain poorly defined. To control the cell types available for regeneration, a genetic model to extensively ablate the uterine epithelium was combined with transplantation of lineage-labeled organoids. Ablation without organoid transplantation triggered re-epithelialization, but resulted in infertility. Transplanted endometrial epithelial organoids engrafted into the ablated uterus, reconstructed both the luminal and glandular epithelia, and restored fertility. Depleting organoids of the glandular lineage before transplantation revealed that luminal epithelial-derived cells acquire glandular identity and function after engraftment. The same luminal-to-glandular epithelial differentiation trajectory emerged during endogenous repair following targeted glandular ablation. Together, these findings establish luminal-to-glandular epithelial conversion as an intrinsic regenerative property of the adult uterine epithelium and establish an endometrial organoid transplantation platform with therapeutic potential.
Related
- Organoid-to-organoid transplantation and pro-neurogenic treatment promote graft integration and neuronal repair in a human ischemic model
- A comparative transcriptomic framework across kidney organoid, assembloid, and transplantation models
- A scalable microarrayed organoid platform for precision modeling of intestinal epithelial damage and recovery
- VIRMA-associated SRD5A2 downregulation promotes BPH progression through ERα-CREB5-dependent epithelial plasticity
- Systemic Analysis of Patient Derived Esophageal Epithelial Organoid Model Reveals Cell State Heterogeneity and Conservation of Differentiation Hierarchy
BibTeX
@misc{mopure2026organoid,
title = {{Organoid transplantation in the adult endometrium restores fertility and uncovers epithelial lineage plasticity}},
author = {D. Mopure and H. I. Kim and C. J. Ang and D. J. Davis and T. E. Spencer and K. L. McKinley and A. M. Kelleher},
howpublished = {bioRxiv},
year = {2026},
month = aug,
doi = {10.64898/2026.08.28.747350},
url = {https://www.biorxiv.org/content/10.64898/2026.08.28.747350v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - Organoid transplantation in the adult endometrium restores fertility and uncovers epithelial lineage plasticity
AU - D. Mopure
AU - H. I. Kim
AU - C. J. Ang
AU - D. J. Davis
AU - T. E. Spencer
AU - K. L. McKinley
AU - A. M. Kelleher
PY - 2026
DA - 2026/08/28
PB - bioRxiv
DO - 10.64898/2026.08.28.747350
UR - https://www.biorxiv.org/content/10.64898/2026.08.28.747350v1
AB - The adult endometrium regenerates repeatedly, yet the cells and mechanisms that rebuild its epithelium remain poorly defined. To control the cell types available for regeneration, a genetic model to extensively ablate the uterine epithelium was combined with transplantation of lineage-labeled organoids. Ablation without organoid transplantation triggered re-epithelialization, but resulted in infertility. Transplanted endometrial epithelial organoids engrafted into the ablated uterus, reconstructed both the luminal and glandular epithelia, and restored fertility. Depleting organoids of the glandular lineage before transplantation revealed that luminal epithelial-derived cells acquire glandular identity and function after engraftment. The same luminal-to-glandular epithelial differentiation trajectory emerged during endogenous repair following targeted glandular ablation. Together, these findings establish luminal-to-glandular epithelial conversion as an intrinsic regenerative property of the adult uterine epithelium and establish an endometrial organoid transplantation platform with therapeutic potential.
ER -