Endometrial cells with high ALDH activity contribute to uterine development and regeneration
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 (ALDH HI cells) were long-lived progenitors in the endometrium with a…
Recent research has shed light on the role of endometrial cells with high ALDH activity in uterine development and regeneration. Adult stem cells are known to be responsible for the regenerative potential of the endometrium, but their specific identity and features have yet to be fully understood. Utilizing both in vivo and in vitro methods, scientists have now demonstrated that cells with high ALDH activity (ALDH HI cells) are long-lived progenitors within the endometrium.
These cells possess enhanced organoid formation capacity, long-term passaging potential, and stemness gene signatures.
Using a specialized mouse model, researchers observed that ALDH1A1 + epithelial cells expanded during postnatal development, while ALDH1A1 + stromal cells expanded during estrous cycling. Both populations of ALDH1A1 + cells were also present during postpartum repair. The spatial localization of these cells is hormone-sensitive; ALDH1A1 + cells localized to glandular crypts of the endometrium in response to ovariectomy or exogenous estradiol. This indicates that their positioning can change depending on hormonal influences.
The functional implications of these findings were also explored. Selective ablation of ALDH1A1 + cells in a mouse model led to a decrease in endometrial gland number and FOXA2 expression. Similar results were observed in human endometrial epithelial organoids with high ALDH activity (ALDH HI cells), which displayed a higher organoid formation capacity than ALDH LO cells. These organoids also had unique transcriptomes, with fewer luminal-like ciliated cells.
In conclusion, these studies reveal that ALDH1A1 + cells are hormone-sensitive adult stem cells within the endometrium, characterized by their regenerative potential. These cells play a critical role in endometrial development and function, making them a key focus for further investigation into the mechanisms of uterine biology.
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