Language
English
Publication Date
8-6-2026
Journal
eLife
DOI
10.7554/eLife.110975
PMID
42559809
PMCID
PMC13446906
PubMedCentral® Posted Date
8-6-2026
PubMedCentral® Full Text Version
Post-print
Abstract
Adult stem cells are thought to drive the regenerative potential of the endometrium and contribute to the pathogenesis of endometriosis; however, their identity and defining features remain to be characterized. Here, we used in vivo and in vitro approaches to demonstrate that cells with high aldehyde dehydrogenase 1 activity (ALDHHI cells) were long-lived progenitors in the endometrium with a higher organoid formation capacity, long-term passaging potential, and stemness gene signatures. Using lineage tracing with an Aldh1a1creERT2/+; Rosa26LSL-tdTomato reporter mouse, Aldh1a1+ epithelial cells expanded during postnatal development, Aldh1a1+ stromal cells expanded during estrous cycling, and both populations of Aldh1a1+ cells were present during postpartum repair. In response to ovariectomy or exogenous estradiol, we found that ALDH1A1+ cells localized to glandular crypts of the endometrium or throughout the luminal epithelium, respectively, indicating that their spatial localization is hormone-sensitive. Functionally, we found that selective ablation of ALDH1A1+ cells in Aldh1a1creERT2/+; Rosa26LSL-DTR mice decreased endometrial gland number and FOXA2 expression. These findings were recapitulated in the human endometrium, where endometrial epithelial organoids with high ALDH activity (ALDHHI cells) showed a higher organoid formation capacity than ALDHLO cells and displayed unique transcriptomes with fewer luminal-like ciliated cells. Overall, our studies indicate that ALDH1A1+ cells are hormone-sensitive adult stem cells in the endometrium with regenerative potential that are critical for endometrial development and function.
Keywords
Female, Animals, Endometrium, Regeneration, Mice, Aldehyde Dehydrogenase 1 Family, Humans, Retinal Dehydrogenase, Uterus, Epithelial Cells
Published Open-Access
yes
Recommended Citation
Tang, Suni; Unser, Anna Catherine; Jiang, Peixin; et al., "Endometrial Cells With High ALDH Activity Contribute to Uterine Development and Regeneration" (2026). Faculty, Staff and Students Publications. 8179.
https://digitalcommons.library.tmc.edu/baylor_docs/8179