Single cell analysis of endometriosis reveals a coordinated transcriptional program driving immunotolerance and angiogenesis across eutopic and ectopic tissues.

Abstract

Endometriosis is characterized by growth of endometrial-like tissue outside of the uterus affecting many women in their reproductive age, causing years of pelvic pain and potential infertility. Its pathophysiology remains largely unknown, limiting diagnosis and treatment. We characterized peritoneal and ovarian lesions at single-cell transcriptome resolution and compared to matched eutopic endometrium, control endometrium, and organoids derived from these tissues, generating data on over 100,000 cells across 12 individuals. We spatially localized many of the cell types using imaging mass cytometry. We identify a perivascular mural cell unique to the peritoneal lesions with dual roles in angiogenesis promotion and immune cell trafficking. We define an immunotolerant peritoneal niche, fundamental differences in eutopic endometrium and between lesions microenvironments, and a novel progenitor-like epithelial cell subpopulation. Altogether, this study provides a holistic view of the endometriosis microenvironment representing the first comprehensive cell atlas of the disease, essential information for advancing therapeutics and diagnostics.

Single-cell analysis in endometrial research

“…(Miltenyi GentleMACS Dissociator) and cold-active proteases or dispases were employed for endometrial biopsy dissociation [51] . Decidua is another type of endometrial biopsy specimen.…”

“…In the second stage, Wang et al digested the remaining tissue using TrypLE Select for 20 min at 37°C with intermittent pipetting homogenization for epithelial cells, whereas Queckbörner et al further digested the tissue using collagenase III and DNASE for 45 min at 37°C with agitation. Recently, a specialized equipment (Miltenyi GentleMACS Dissociator) and cold-active proteases or dispases were employed for endometrial biopsy dissociation [51] . Decidua is another type of endometrial biopsy specimen.…”

“…Moreover, fewer activated T cells, a decreased percentage of NK cells, and an increased proportion of macrophages were observed in endometriosis. The unique immune microenvironment of endometriotic lesions might be caused by the unique perivascular mural cells in endometriotic lesions, which affect immune cell trafficking [51] .…”