The Biological Characteristics of Eutopic and Ectopic EndometrialProgenitor Cells in Endometriosis

In: Current Stem Cell Research & Therapy · 2023 · vol. 18(8) , pp. 1172–1183 · doi:10.2174/1574888x18666230203162452 · W4319294712
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This study isolated endometrial progenitor cells from eutopic and ectopic tissues of endometriosis patients, finding that ectopic cells exhibit strong clonogenicity and progesterone resistance, with differentially expressed genes related to metabolism and immune response.

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This study isolated epithelial progenitor (EP) cells and endometrial mesenchymal stem cells (eMSCs) from paired eutopic and ectopic endometrial tissues of endometriosis patients, assessing cell distribution and steroid hormone receptor expression by immunohistochemistry and sorting EP/eMSC populations for functional assays (clonogenicity, viability under estradiol/progesterone) plus marker expression and RNA sequencing. The authors found SSEA-1– and PDGFRβ-positive cells in epithelial and stromal layers, with stronger ERβ staining in ectopic tissues and nearly absent PR expression, alongside ectopic EP cells showing strong clonogenicity and ERβ expression but weak PR expression consistent with progesterone resistance. RNA-seq identified thousands of differentially expressed genes between eutopic and ectopic EP cells or eMSCs, with enriched pathways for cellular energy metabolism and immune response regulation, and ERβ targets enriched in ectopic EP cells. The paper’s limitation, as stated in scope, is that its conclusion about lesion formation is based on ex vivo/in vitro characterization rather than direct in vivo demonstration of ectopic lesion development. This paper is centrally about endometriosis — it characterizes eutopic versus ectopic endometrial progenitor cell biology (EP cells and eMSCs) and their hormone-receptor–linked metabolism/immune changes that may contribute to ectopic lesion formation.

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Abstract

Aim: The aim of this study was to identify the biological characteristics and potential roles of endometrial progenitor cells in the pathogenesis of endometriosis. Background: It is generally believed that progenitor cells in human endometrium are responsible for rapid endometrial regeneration. However, the biological characteristics and potential roles of the paired eutopic and ectopic endometrial progenitor cells in endometriosis remain unclear. Objective: This study intends to isolate the epithelial progenitor (EP) cells and endometrial mesenchymal stem cells (eMSCs) from the eutopic and ectopic endometria from endometriosis patients, further to reveal their features and functions respectively. Methods: The distributions of EP cells and eMSCs and the expression of steroid hormone receptors in the endometrium and endometriotic tissues were assessed by immunohistochemistry. EP cells and eMSCs were sorted from paired eutopic and ectopic endometria with epithelial cell adhesion molecule (EpCAM) magnetic beads. The clonogenicity, cell viability after being treated with estradiol and progesterone, and cell markers expression were evaluated with colony forming on Matrigel, CCK-8 and immunofluorescence staining, respectively. The differentially expressed genes (DEGs) were further identified with RNA sequencing. Results: SSEA-1- and PDGFRβ-positive cells were distributed in the epithelial and stromal layers. The ERβ staining was much more intense in endometriotic tissues, but PR expression was almost absent. The ectopic EP cells exhibit strong clonogenicity and ERβ expression but weak PR expression, leading to progesterone resistance. There are 12604 and 13242 DEGs revealed by RNA sequencing between eutopic and ectopic EP cells or eMSCs. GO and KEGG analyses revealed that the functions and pathways of DEGs enriched in cellular energy metabolism and regulation of the immune response, respectively. Additionally, ERβ targets were mainly enriched in ectopic EP cells. Conclusion: Both EP cells and eMSCs may engage in ectopic lesion formation in endometriosis by modifying the metabolic mode and immune tolerance. These data not only help to understand the molecular mechanism of endometriosis but also could potentially contribute to the discovery of therapeutic targets for endometriosis.
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Abstract

Aim: The aim of this study was to identify the biological characteristics and potential roles of endometrial progenitor cells in the pathogenesis of endometriosis.

Background

It is generally believed that progenitor cells in human endometrium are responsible for rapid endometrial regeneration. However, the biological characteristics and potential roles of the paired eutopic and ectopic endometrial progenitor cells in endometriosis remain unclear.

Objective

This study intends to isolate the epithelial progenitor (EP) cells and endometrial mesenchymal stem cells (eMSCs) from the eutopic and ectopic endometria from endometriosis patients, further to reveal their features and functions respectively.

Methods

The distributions of EP cells and eMSCs and the expression of steroid hormone receptors in the endometrium and endometriotic tissues were assessed by immunohistochemistry. EP cells and eMSCs were sorted from paired eutopic and ectopic endometria with epithelial cell adhesion molecule (EpCAM) magnetic beads. The clonogenicity, cell viability after being treated with estradiol and progesterone, and cell markers expression were evaluated with colony forming on Matrigel, CCK-8 and immunofluorescence staining, respectively. The differentially expressed genes (DEGs) were further identified with RNA sequencing.

Results

SSEA-1- and PDGFRβ-positive cells were distributed in the epithelial and stromal layers. The ERβ staining was much more intense in endometriotic tissues, but PR expression was almost absent. The ectopic EP cells exhibit strong clonogenicity and ERβ expression but weak PR expression, leading to progesterone resistance. There are 12604 and 13242 DEGs revealed by RNA sequencing between eutopic and ectopic EP cells or eMSCs. GO and KEGG analyses revealed that the functions and pathways of DEGs enriched in cellular energy metabolism and regulation of the immune response, respectively. Additionally, ERβ targets were mainly enriched in ectopic EP cells.

Conclusion

Both EP cells and eMSCs may engage in ectopic lesion formation in endometriosis by modifying the metabolic mode and immune tolerance. These data not only help to understand the molecular mechanism of endometriosis but also could potentially contribute to the discovery of therapeutic targets for endometriosis.

Keywords

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