TY - JOUR KW - WNT7A KW - endometrium KW - Epithelial Cells KW - luminal epithelium KW - Menstrual Cycle KW - menstruation KW - organoids KW - Regeneration KW - Transcriptomics KW - wound healing AU - Konstantina Nikolakopoulou AU - Weand Ybañez AU - Lhéanna Klaeylé AU - Lisa Frugoli AU - Tereza Cindrova-Davies AU - Hans-Rudolf Hotz AU - Charlotte Soneson AU - Margherita Yayoi Turco AB - Menstruation is an unusual process in which the human endometrium undergoes cyclical shedding with scarless regeneration. Despite its pivotal role in reproductive health, the cellular states and interactions orchestrating this process remain poorly defined, largely due to the lack of in vitro systems that capture the inaccessible perimenstrual window. We use human endometrial organoids to establish an in vitro menstrual cycle (IVMC) protocol that recapitulates cyclical epithelial dynamics. We validate the IVMC by benchmarking against in vivo samples spanning the menstrual window through histology, transcriptomic, and multiplex secreted-protein analysis. During menstruation, the in vivo luminal epithelium acquires a distinct transcriptomic signature, characterized by WNT7A expression. Loss of WNT7A compromises long-term organoid survival, highlighting its functional importance. The regeneration-associated luminal epithelium acts as a signaling hub during regeneration through interactions with the vasculature. This work opens new avenues to dissect the unique regenerative program of the endometrium in health and disease. BT - Cell Stem Cell DA - 2026-04-28 DO - 10.1016/j.stem.2026.04.005 N2 - Menstruation is an unusual process in which the human endometrium undergoes cyclical shedding with scarless regeneration. Despite its pivotal role in reproductive health, the cellular states and interactions orchestrating this process remain poorly defined, largely due to the lack of in vitro systems that capture the inaccessible perimenstrual window. We use human endometrial organoids to establish an in vitro menstrual cycle (IVMC) protocol that recapitulates cyclical epithelial dynamics. We validate the IVMC by benchmarking against in vivo samples spanning the menstrual window through histology, transcriptomic, and multiplex secreted-protein analysis. During menstruation, the in vivo luminal epithelium acquires a distinct transcriptomic signature, characterized by WNT7A expression. Loss of WNT7A compromises long-term organoid survival, highlighting its functional importance. The regeneration-associated luminal epithelium acts as a signaling hub during regeneration through interactions with the vasculature. This work opens new avenues to dissect the unique regenerative program of the endometrium in health and disease. PY - 2026 T2 - Cell Stem Cell TI - An in vitro menstrual cycle using organoids captures epithelial cell transitions during menstruation and regeneration of the human endometrium UR - https://www.sciencedirect.com/science/article/pii/S1934590926001451 Y2 - 2026-05-04 SN - 1934-5909 ER -