Single-cell atlas reveals immune microenvironment heterogeneity in endometriosis subtypes

Endometriosis affects an estimated 10% of women within the reproductive age group globally, causing chronic pelvic pain and infertility. Nevertheless, its cellular and molecular pathogenic mechanisms remain poorly understood. This research performed a systematic analysis of three eutopic endometrium specimens, three ovarian endometriosis specimens, and three deep infiltrating endometriosis specimens, utilizing the GSE213216 single-cell RNA sequencing dataset. The study successfully established a detailed single-cell atlas that delineates the cellular composition of endometrial epithelial cells, stromal cells, and diverse immune cell populations. This study demonstrates tissue-specific heterogeneity in cell-subset distribution and transcriptional states, reflecting profound cellular remodeling and reprogramming in disease. Endometriotic microenvironments exhibit robust immune activation; most pronounced in deep infiltrating endometriosis. Epithelial cells upregulate antigen presentation and oxidative phosphorylation. Cell crosstalk is subtype-dependent: immune cells predominantly interact with ciliated epithelial cells in ovarian endometriosis and with glandular secretory cells in deep infiltrating endometriosis. We further identify increased infiltration of TAGLN⁺ fibroblasts linked to tissue fibrosis. This investigation comprehensively elucidates the intricate complexity and substantial heterogeneity of the immune microenvironment across distinct endometriosis subtypes through single-cell resolution analysis. The single-cell dissection reveals inter-subtype microenvironmental complexity, providing mechanistic insights and theoretical basis to advance precise diagnosis and targeted therapies for endometriosis.