Characterising the niche of endometrial stem/progenitor cells in endometriosis

We discovered 2 types of adult stem cells in human endometrium – epithelial progenitor and mesenchymal stem cell (eMSC) - likely responsible for its regeneration each month during the menstrual cycle. We also identified specific surface markers of the epithelial progenitor (N-cadherin) and eMSC: SUSD2. Epithelial progenitors are found in the bases of the glands adjacent to the myometrium (uterine muscle) and eMSC have a perivascular location. Another set of markers CD146 and PDGFR-β showed that the eMSC are pericytes, located adjacent to the endothelial cells. In a sheep model, we found that CD271+ eMSC are also perivascular, located in the adventitia of larger vessels rather than pericytes. N-cadherin+ and SUSD2+ cells are shed during menstruation and are found in greater numbers in the pelvic cavity of women with endometriosis compared to normal, likely contributing to its pathogenesis. This project will undertake a detailed analysis of human and monkey endometrium, adenomyosis and endometriosis lesions using sophisticated confocal microscopy to determine the precise locations of endometrial epithelial progenitors, eMSC and their niche cells. Colocalisation with other stem cell markers (SSEA-1, OCT4, SOX2, NANOG, Notch-1, Lgr5, Musashi-1) and estrogen and progesterone receptors from normal and endometriosis women will also be examined. This project will generate beautiful images showing precisely where epithelial progenitors and eMSC reside in endometrial tissue and in endometriosis lesions, providing insight into the role of endometrial stem/progenitor cells in endometriosis.