Abstract
BackgroundAdenomyosis (AM) is a common benign chronic gynaecological disorder; however, the precise pathogenesis of adenomyosis is still poorly understood. Single-cell RNA sequencing (scRNA-seq) can uncover rare subpopulations, explore genetic and functional heterogeneity, and reveal the uniqueness of each cell. It provides us a new approach to reveal biological issues from a more detailed and microscopic perspective. Here, we utilize this revolutionary technology to identify the changes of gene expression patterns between ectopic lesions and the eutopic endometrium at the single-cell level and explore a potential novel pathogenesis of AM.MethodsA control endometrium (sample with leiomyoma excluding endometrial disorders, n = 1), eutopic endometrium and ectopic lesion (from a patient with adenomyosis, n = 1) samples were analysed by scRNA-seq, and additional leiomyoma (n = 3) and adenomyosis (n = 3) samples were used to confirm colocalization and vasculogenic mimicry (VM) formation. Protein colocalization was visualized by immunofluorescence, and CD34-periodic acid-Schiff (PAS) double staining was used to assess the formation of VM.ResultsThe scRNA-seq results suggest that cancer-, cell motility- and inflammation- (CMI) associated terms, cell proliferation and angiogenesis play important roles in the progression of AM. Moreover, the colocalization of EPCAM and PECAM1 increased significantly in the ectopic endometrium group (P < 0.05), cell subpopulation with high copy number variation (CNV) levels possessing tumour-like features existed in the ectopic lesion sample, and VNN1- and EPCAM-positive cell subcluster displayed active cell motility in endometrial epithelial cells. Furthermore, during the transformation of epithelial cells to endothelial cells, we observed the significant accumulation of VM formation (positively stained with PAS but not CD34, P < 0.05) in ectopic lesions.ConclusionsIn the present study, our results support the theory of adenomyosis derived from the invasion and migration of the endometrium. Moreover, cell subcluster with high CNV level and tumour-associated characteristics is identified. Furthermore, epithelial-endothelial transition (EET) and the formation of VM in tumours, the latter of which facilitates the blood supply and plays an important role in maintaining cell growth, were also confirmed to occur in AM. These results indicated that the inhibition of EET and VM formation may be a potential strategy for AM management.
Highlights
Adenomyosis (AM) is a common benign chronic gynaecological disorder; the precise pathogenesis of adenomyosis is still poorly understood
Liu et al Cell Biosci (2021) 11:51 which facilitates the blood supply and plays an important role in maintaining cell growth, were confirmed to occur in AM. These results indicated that the inhibition of endothelial transition (EET) and vasculogenic mimicry (VM) formation may be a potential strategy for AM management
Eutopic endometrium (AM_EM group) and ectopic endometrium (AM_EC group) samples were obtained from total hysterectomies of patients with AM, and endometrial tissue from patients with hysteromyoma served as the control (AM_CTRL group)
Summary
Adenomyosis (AM) is a common benign chronic gynaecological disorder; the precise pathogenesis of adenomyosis is still poorly understood. It provides us a new approach to reveal biological issues from a more detailed and microscopic perspective. We utilize this revolutionary technology to identify the changes of gene expression patterns between ectopic lesions and the eutopic endometrium at the single-cell level and explore a potential novel pathogenesis of AM. There is evidence showing that the incidence rate has presented an increasing trend because of the optimization of diagnostic imaging techniques such as transvaginal ultrasound scan (TVUS) and magnetic resonance imaging (MRI), and the increased proportion of young women diagnosed is remarkable [5, 6]. The diagnostic criteria for imaging have not been unified
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