Single-cell atlas of the leiomyoma microenvironment reveals hallmarks of myometrial vascular inflammation

Uterine fibroids or leiomyoma are benign smooth muscle-derived tumours and are the most common pelvic uterine tumours of women in reproductive age. Large numbers of patients present with symptoms of heavy or prolonged menstrual bleeding, dyspareunia, pelvic pain, miscarriage, and infertility. The underlying causes are not understood; however it is hypothesized that fibroid-uterine interactions orchestrate clinical sequelae, mediated through the pseudocapsule, an anatomical entity that surrounds the myoma and separates it from normal myometrium. We here present a single cell atlas of the uterine pseudocapsule architecture by integrating single nuclei transcriptomics with highly multiplexed immunofluorescence imaging. The data suggest vascular inflammation leading to substantial infiltration of activated innate and adaptive immune cells in the pseudocapsule and we map fibroblast/stromal and endothelial cell activation states and interactions. The results advance our understanding of molecular events underlying leiomyoma pathology and provide novel insights into aberrant and actionable immunological processes occurring in the tumour microenvironment.