Dislodged dual progenitors for endometrial epithelia and stroma can cause endometriosis

The inner surface of the uterus is lined by a specialized layer called the endometrium, composed primarily of epithelial glands surrounded by supportive stroma. The human endometrium undergoes approximately 500 cycles of regeneration and breakdown over the course of a woman's reproductive life, suggesting that a pool of endometrial progenitor cells must exist. However to date, little is known about the markers or hierarchy of human endometrial progenitors. In order to identify a potential progenitor in the endometrium, we isolated human endometrial cells based on two cell surface markers, Trop1 and CD10, that are found on endometrial epithelia and stroma respectively. My hypothesis was that cells positive for both markers were the dual progenitor of epithelia and stroma in the human endometrium. First we used IHC staining to demonstrate that these dual positive cells exist and are located at the bases and junctions of epithelial glands. We then isolated these cells and plated them as single cells in vitro. We found that dual positive cells could differentiate into epithelia and stroma, but a different population of cells expressing the epithelial marker alone could only produce epithelia, and a cell population expressing the stromal marker alone could only give rise to stroma. We also developed an in vivo assay for dissociated mouse uterine cells and adapted that for human cells. My in vivo results were inconclusive, and repeated experiments could no regenerate a human epithelial gland in vivo. However the in vitro results are promising and seem to show that these dual positive cells can give rise to both epithelia and stroma in vitro. This suggests that these dual positive cells contain the dual progenitor for epithelia and stroma in the human endometrium, a cell population that has not been previously identified. This dual progenitor population may play a role in the origin and dissemination of endometriosis, a common and painful gynecological disease where endometrial lining implants and cycles on other organs. In order to explore the link between this cell population and endometriosis, we analyzed the endometrial tissue and pelvic washing cells from women with endometriosis. My initial results seem to show an increased percentage of dual positive cells in endometrial tissue of women with endometriosis, and that these cells were present in the abdominal cavity of women with and without endometriosis. More work needs to be done, but it is possible that these dual positive cells are the source the progenitors that play a role in the pathogenesis of the disease. Identification and characterization of this population is part of a long term project in my laboratory to understand the hierarchy of cells in the endometrium and how dysregulation contributes to disease states. More work needs to be done to determine whether these dual positive cells can regenerate epithelia and stroma in vivo, whether there is a difference between dual positive cells in patients with and without endometriosis, and if so, what are the genetic pathways involved in the aberrant differentiation of cells that cause disease.