Altered Differentiation of Endometrial Mesenchymal Stromal Fibroblasts is Associated with Endometriosis Susceptibility

Overview

Journal Commun Biol

Specialty Biology

Date 2022 Jun 20

PMID 35725766

Authors

Brett D McKinnon

Samuel W Lukowski

Sally Mortlock

Joanna Crawford

Sharat Atluri

Sugarniya Subramaniam

Rebecca L Johnston

Konstantinos Nirgianakis

Keisuke Tanaka

Akwasi Amoako

Michael D Mueller

Grant W Montgomery

Affiliations

Soon will be listed here.

Abstract

Cellular development is tightly regulated as mature cells with aberrant functions may initiate pathogenic processes. The endometrium is a highly regenerative tissue, shedding and regenerating each month. Endometrial stromal fibroblasts are regenerated each cycle from mesenchymal stem cells and play a pivotal role in endometriosis, a disease characterised by endometrial cells that grow outside the uterus. Why the cells of some women are more capable of developing into endometriosis lesions is not clear. Using isolated, purified and cultured endometrial cells of mesenchymal origin from 19 women with (n = 10) and without (n = 9) endometriosis we analysed the transcriptome of 33,758 individual cells and compared these to clinical characteristics and in vitro growth profiles. We show purified mesenchymal cell cultures include a mix of mesenchymal stem cells and two endometrial stromal fibroblast subtypes with distinct transcriptomic signatures indicative of varied progression through the differentiation processes. The fibroblast subgroup characterised by incomplete differentiation was predominantly (81%) derived from women with endometriosis and exhibited an altered in vitro growth profile. These results uncover an inherent difference in endometrial cells of women with endometriosis and highlight the relevance of cellular differentiation and its potential to contribute to disease susceptibility.

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