The endometrium, the uterine mucosa, changes dynamically in response to ovarian hormones throughout the menstrual cycle. Researchers created rich single-cell and spatial reference maps of the human uterus, as well as three-dimensional endometrial organoids. They investigated the signaling networks that govern cell fate in the lumenal and glandular microenvironments. Their endometrial organoids benchmark exposes the pathways and cell states that regulate secretory and ciliated lineage development both in vivo and in vitro. Downregulation of WNT or NOTCH pathways in vitro improves differentiation efficiency along secretory and ciliated lineages, respectively. The researchers used cellular maps to deconvolute bulk data from endometrial malignancies and endometriotic lesions, highlighting the cell types that predominate in each of these illnesses. These mechanistic discoveries provide the groundwork for the future development of medicines for prevalent illnesses such as endometriosis and endometrial cancer.