Single-Cell RNA Sequencing Shows Markedly Elevated Immune Cell Proportions in the Endometrium of Women with Endometriosis—A Narrative Review

Muhammad A. Riaz, Felix Zeppernick, Magdalena Zeppernick, Ivo Meinhold‐Heerlein, Lutz Konrad
In: International Journal of Molecular Sciences · 2026 · vol. 27(16) , pp. 7440 · doi:10.3390/ijms27167440 · W7203787009
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This narrative review uses single-cell RNA sequencing to demonstrate that immune cell dysregulation, particularly increased macrophages, drives endometriosis pathogenesis alongside endothelial and myofibroblast involvement in angiogenesis and fibrosis.

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Abstract

Single-cell RNA sequencing is a state-of-the-art approach to decipher the heterogeneity of RNA transcripts in individual cells and identify different cell types in tissues and organs. Its aim is to create a high-resolution cell atlas to better understand organs and diseases. In this narrative review, we focus on the main endometrial cell types and their possible significance in endometriosis. Examination of the normal endometrium (NEM), eutopic endometrium of patients (EUE) and ectopic endometrium (EMS) revealed a predominance of endometrial stromal cells (ESCs), followed by epithelial cells (EECs), immune cells (ICs), endothelial cells (ECs) and pericytes (PVs). Comparison of the NEM with the EUE showed only minor changes in ESC and EEC proportions, but a dramatic increase in ICs in EUE, especially uterine macrophages (uM1). The ESC-IC homeostasis was especially disturbed. In EMS a marked reduction in EEC and NK cell proportions was found, accompanied by a significant increase in ECs and M2 macrophages. Furthermore, in EMS a significant shift from fibroblasts (Fibs) to myofibroblasts (MyoFibs), indicating fibrosis, was reported. Of note, ESC/EEC stem cells were described only very rarely, while nerve cells were not detected. In summary, scRNA-seq provided a good description of the cell proportions in NEM and EUE, but further studies are needed to analyze EMS. In conclusion, strong evidence supports the critical importance of ICs and immune system dysregulation in initiation and of ECs and MyoFibs in angiogenesis and fibrosis, respectively, in the pathogenesis of endometriosis.

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