Single Cell atlas of uterine myometrium and leiomyomas reveals diverse and novel cell types of non-monoclonal origin

Abstract

Uterine leiomyomas are the most common tumors of the female reproductive tract with significant morbidity that includes excessive bleeding, infertility and pregnancy complications. The origin and cellular composition of leiomyomas is controversial, yet very important in better understanding the pathogenesis of these tumors. We applied single-cell RNA sequencing to better understand cellular heterogeneity of uterine leiomyomas and normal myometrium at the molecular level. Our data reveal previously unknown heterogeneity in the smooth muscle cells, fibroblast cells, and endothelial cells of normal myometrium and leiomyomas. We discovered a novel lymphatic endothelial cell population in uterine leiomyomas and that the immune as well as transcriptional profile of leiomyomas is MED12 genotype-dependent. Moreover, we show that leiomyoma cell moiety is not monoclonal in nature. Our work describes unprecedented single cell resolution of normal uterine myometrium and leiomyoma tumors and provides insight into tumor specific hormone responsiveness and extracellular matrix accumulation.

Markers of Inflammation and Vascular Parameters in Selective Progesterone Receptor Modulator (Ulipristal Acetate)-Treated Uterine Fibroids

“…These monoclonal tumors are formed in smoothmuscle cells due to a variety of reasons. At this point, it is worth mentioning that, although the majority of existing literature sources consider UFs monoclonal in nature, most recent studies point towards the possibility of leiomyoma as being heterogenous and consisting of diverse and novel cell types (single cell RNA sequencing analysis in MED12 (+) and MED12 (−) variants of leiomyomas) [1]. A combination of severe hypoxia and gonadal steroids stimulates the local expression of the angiogenic growth factor in fibroid tissue, as well as the production of cytokines and chemokines.…”