The heterogeneity of fibrosis and angiogenesis in endometriosis revealed by single-cell RNA-sequencing.

Fibrosis, angiogenesis and chronic inflammation are the inherent characteristics of endometriosis (EMS). The cellular heterogeneity of ectopic and non-ectopic endometrium by single-cell RNA-sequencing (scRNA-seq)at secretory phase without the disturbance of hormone drugs hasn't been explored so far. In this study, scRNA-seq was adopted to explore the properties of ectopic endometrium (ECE), eutopic endometrium (EUE) and normal endometrium (NOE) at secretory phase. We found that (i) The proportion of myofibroblasts, pericytes, endothelial cells and macrophages in ECE overwhelms that of non-ectopic tissues (EUE and NOE), and Myofibro.C2 was the predominant myofibroblast sub-cluster in ECE. (ii) Myofibroblasts were mainly fibroblast-to-myofibroblast transdifferentiation (FMT) and pericytes were endothelial cell-dependent differentiation in ECE. (iii) Both myofibroblasts and pericytes had a low differentiation potential. (iv) The increased inflammation score, deceased NK cells, T cell exhaustion score and antigen-presenting capacity in ECE confirmed the inflammatory properties and immunodeficiency of ECE. These findings suggested that myofibroblasts, pericytes and macrophages may be the potential targets for anti-fibrotic, anti-angiogenic and anti-inflammatory therapy of EMS.