02125nas a2200325   4500000000100000008004100001260001500042653001000057653001600067653002100083653002300104653002000127653001700147653001400164653001700178653002000195653001800215100003100233700001800264700002200282700001700304700002700321700002100348700002200369700002700391245015400418856007200572520114100644022001401785       2026                            d  c2026-04-2810aWNT7A10aendometrium10aEpithelial Cells10aluminal epithelium10aMenstrual Cycle10amenstruation10aorganoids10aRegeneration10aTranscriptomics10awound healing1 aKonstantina Nikolakopoulou1 aWeand Ybañez1 aLhéanna Klaeylé1 aLisa Frugoli1 aTereza Cindrova-Davies1 aHans-Rudolf Hotz1 aCharlotte Soneson1 aMargherita Yayoi Turco00aAn <i>in vitro</i> menstrual cycle using organoids captures epithelial cell transitions during menstruation and regeneration of the human endometrium  uhttps://www.sciencedirect.com/science/article/pii/S19345909260014513 aMenstruation 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.  a1934-5909