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Whole-Tissue Deconvolution and scRNAseq Analysis Identify Altered Endometrial Cellular Compositions and Functionality Associated With Endometriosis.

ABSTRACT: The uterine lining (endometrium) exhibits a pro-inflammatory phenotype in women with endometriosis, resulting in pain, infertility, and poor pregnancy outcomes. The full complement of cell types contributing to this phenotype has yet to be identified, as most studies have focused on bulk tissue or select cell populations. Herein, through integrating whole-tissue deconvolution and single-cell RNAseq, we comprehensively characterized immune and nonimmune cell types in the endometrium of women with or without disease and their dynamic changes across the menstrual cycle. We designed metrics to evaluate specificity of deconvolution signatures that resulted in single-cell identification of 13 novel signatures for immune cell subtypes in healthy endometrium. Guided by statistical metrics, we identified contributions of endometrial epithelial, endothelial, plasmacytoid dendritic cells, classical dendritic cells, monocytes, macrophages, and granulocytes to the endometrial pro-inflammatory phenotype, underscoring roles for nonimmune as well as immune cells to the dysfunctionality of this tissue.

SUBMITTER: Bunis DG

PROVIDER: S-EPMC8766492 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Altered differentiation of endometrial mesenchymal stromal fibroblasts is associated with endometriosis susceptibility.

Project description: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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Endometrial methylome of patients without endometriosis

Project description:Alterations in endometrial DNA methylation profile have been proposed as one potential mechanism initiating the development of endometriosis. However, the normal endometrial methylome is influenced by the cyclic hormonal changes and the menstrual cycle phase-dependent epigenetic signature should be considered when studying endometrial disorders. So far, no studies have been performed to evaluate the menstrual cycle influences and endometriosis-specific endometrial methylation pattern at the same time. Therefore, we used Infinium HumanMethylation 450K BeadChip arrays to explore DNA methylation profiles of endometrial tissues from various menstrual cycle phases. Infinium HumanMethylation 450K BeadChip arrays were used to explore DNA methylation profiles of endometrial tissues from mid secretory cycle phase from 17 patients without endometriosis

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Endometrial methylome of patients with endometriosis

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Endometrial Cancer Incidence in Endometriosis and Adenomyosis.

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Endometrial methylome of patients without endometriosis

2016-02-15 | GSE73949 | GEO

Endometrial methylome of patients with endometriosis

2016-02-15 | GSE73948 | GEO

Transcriptomic deconvolution of human endometrial cell types

Project description:The human endometrium is a highly heterogeneous tissue comprising multiple cell-types and cellular states that change in cycle-dependent manner. This tissue heterogeneity is a major drawback when interpreting bulk (whole biopsy) transcriptomic data. To address this hurdle, RNA-seq analysis was performed on four isolated stromal cell populations [SUSD2+ perivascular stromal cells (PVCs), endometrial stromal cells (EnSCs), SUSD2+ clonal cells (MSCs), and clonal transit amplifying cells (TAs)], glandular epithelial cells, uNK cells, and matched whole tissue. Transcriptomic data were obtained for 3 whole endometrial biopsies and 6 matched, purified cell populations.

2020-10-09 | GSE159266 | GEO

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