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

Daniel Bunis, Daniel G Bunis, Wanxin Wang, Júlia Vallvé-Juanico, Sahar Houshdaran, Sushmita Sen, Isam Ben Soltane, Idit Kosti, Kim Chi Vo, Juan C Irwin, Linda C Giudice, Marina Sirota
Frontiers in immunology · 2022 · vol. 12 , pp. 788315 · doi:10.3389/fimmu.2021.788315 · PMID:35069565 · W4225725145
article OA: gold CC0 ⤵ 36 in-corpus citations
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⚙ AI-generated summary by claude@2026-06, 2026-06-07 ⓘ

This study integrated whole-tissue deconvolution and single-cell RNAseq to identify endometrial epithelial, endothelial, and immune cell types contributing to a pro-inflammatory phenotype in women with endometriosis.

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⚙ AI-generated deep summary by claude@2026-06, 2026-06-07 ⓘ

This study integrated whole-tissue deconvolution (xCell) with microarray differential expression and single-cell RNA-seq to map immune and nonimmune cellular composition changes in human eutopic endometrium across menstrual cycle phases in women with endometriosis versus controls. Using processed public microarray data (105 samples across stages I–IV and proliferative/early-to-mid-secretory phases), it found endometriosis-associated dysregulation of immune pathways, including interferon alpha/gamma responses, TGF-beta/IL-2–STAT5 signaling, and complement activation, with phase- and stage-specific gene differences. For deconvolution, the authors evaluated 64 cell-type signatures for endometrial applicability using permutation testing, scRNA-seq-based specificity metrics in healthy endometrium, and mixture validations, then identified statistically significant contributions from multiple immune and nonimmune cell types (including epithelial/endothelial and several immune subtypes) to a pro-inflammatory endometrial phenotype, while noting that arbitrary differential-expression cutoffs and phase stratification can amplify observed differences. This paper is centrally about endometriosis—specifically, computationally defining how altered endometrial cellular composition and function across the menstrual cycle contribute to the endometriosis-associated pro-inflammatory phenotype.

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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.

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Condition tags

mesh:D004715endometriosisinfertility

MeSH descriptors

Endometriosis Endometriosis Endometriosis Endometriosis Endometrium Endometrium Endometrium RNA-Seq Single-Cell Analysis Female Humans

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Papers in the corpus that this work cites (lower rings, blue) and that cite this one (upper rings, green). Dot size scales with the paper's in-corpus citation count — bigger dot = more influential within the endo/adeno field. Click a dot to open that paper. [ expand to 2 hops ] — adds papers reached through this work's immediate citers/citees. Heavier; up to 60 extra dots.

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