Single-cell transcriptomic atlas of different endometriosis indicating that an interaction between endometriosis-associated mesothelial cells (EAMCs) and ectopic stromal cells may influence progesterone resistance

IF 7.9 1区医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL

Clinical and Translational Medicine Pub Date : 2025-02-19 DOI:10.1002/ctm2.70216

Shengdi Hou, Jing Zhang, Zhiqiang Zhang, Hong Qu, Shuhong Li, Ying Jiang, Chongdong Liu

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Abstract

Background

Endometriosis is a hormone-dependent disease, which can usually be divided into peritoneal endometriosis (PEM), deep-infiltrating endometriosis (DIE) and ovarian endometriosis (OEM). Although the three pathologic types are essentially the same disease, they differ in pathological manifestations, molecular features, pain symptoms and hormonal responsiveness. However, there is limited literature focusing on the differences among these types. In this study, we employed single-cell RNA sequencing (scRNA-seq) to profile the transcriptome of each type using surgical biopsy samples obtained from six patients. We aimed to explore and elucidate the variations among these different types of endometriosis.

Results

We identified five major cell types and 44 subpopulations, including the presence of mesothelial cells in all pathological types, including OEM. Furthermore, we characterised the variations in cell types across different pathological types by employing enrichment analysis to assess functions and pathways. Notably, our findings reveal distinct levels of epithelial–mesenchymal transition (EMT) processes experienced by mesothelial cells within the microenvironment of endometriotic lesions. Through ligand–receptor analysis and referencing relevant literature, we propose that mesothelial cells exert an influence on progesterone resistance in stromal cells through intercellular communication mediated by the FN1-AKT pathway.

Conclusions

Our study comprehensively characterises the heterogeneity of the different pathologic types of endometriosis and offers valuable insights into the underlying mechanisms contributing to variations in progesterone resistance across the three subtypes.

Key points

Single-cell RNA (ScRNA) atlas across types of endometriosis is established.
Mesothelial cells are founded in ovarian endometriosis.
Endometriosis-associated mesothelial cells (EAMCs) experience various level of epithelial–mesenchymal transition (EMT) process in different subtypes.
EAMCs may exert an influence on progesterone resistance in stromal cells through intercellular communication mediated by the FN1-AKT pathway.

Abstract Image

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不同子宫内膜异位症的单细胞转录组图谱表明子宫内膜异位症相关间皮细胞（EAMCs）和异位基质细胞之间的相互作用可能影响黄体酮抵抗

子宫内膜异位症是一种激素依赖性疾病，通常可分为腹膜子宫内膜异位症（PEM）、深浸润性子宫内膜异位症（DIE）和卵巢子宫内膜异位症（OEM）。虽然这三种病理类型本质上是同一种疾病，但它们在病理表现、分子特征、疼痛症状和激素反应性等方面存在差异。然而，关注这些类型之间差异的文献有限。在这项研究中，我们使用单细胞RNA测序（scRNA-seq）来分析来自6名患者的手术活检样本中每种类型的转录组。我们的目的是探讨和阐明这些不同类型的子宫内膜异位症之间的差异。我们确定了5种主要的细胞类型和44个亚群，包括在所有病理类型中都存在间皮细胞，包括OEM。此外，我们通过使用富集分析来评估功能和途径，表征了不同病理类型中细胞类型的变化。值得注意的是，我们的研究结果揭示了子宫内膜异位症病变微环境中间皮细胞经历的不同水平的上皮-间质转化（EMT）过程。通过配体受体分析并参考相关文献，我们提出间皮细胞通过FN1-AKT通路介导的细胞间通讯影响基质细胞的孕酮耐药。结论：我们的研究全面表征了不同病理类型子宫内膜异位症的异质性，并为三种亚型黄体酮耐药性变化的潜在机制提供了有价值的见解。建立了不同类型子宫内膜异位症的单细胞RNA （ScRNA）图谱。间皮细胞见于卵巢子宫内膜异位症。子宫内膜异位症相关间质细胞（EAMCs）在不同亚型中经历不同水平的上皮-间质转化（EMT）过程。EAMCs可能通过FN1-AKT通路介导的细胞间通讯影响基质细胞的孕酮抵抗。

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来源期刊

Clinical and Translational Medicine Multiple-

CiteScore

15.90

自引率

1.90%

发文量

450

审稿时长

4 weeks

期刊介绍： Clinical and Translational Medicine (CTM) is an international, peer-reviewed, open-access journal dedicated to accelerating the translation of preclinical research into clinical applications and fostering communication between basic and clinical scientists. It highlights the clinical potential and application of various fields including biotechnologies, biomaterials, bioengineering, biomarkers, molecular medicine, omics science, bioinformatics, immunology, molecular imaging, drug discovery, regulation, and health policy. With a focus on the bench-to-bedside approach, CTM prioritizes studies and clinical observations that generate hypotheses relevant to patients and diseases, guiding investigations in cellular and molecular medicine. The journal encourages submissions from clinicians, researchers, policymakers, and industry professionals.