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

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 s...

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Bibliographic Details
Published in:Frontiers in immunology 2022-01, Vol.12, p.788315
Main Authors: Bunis, Daniel G, Wang, Wanxin, Vallvé-Juanico, Júlia, Houshdaran, Sahar, Sen, Sushmita, Ben Soltane, Isam, Kosti, Idit, Vo, Kim Chi, Irwin, Juan C, Giudice, Linda C, Sirota, Marina
Format: Article
Language:English
Subjects:
bulk tissue transcriptomics
deconvolution
endometriosis
Endometriosis - genetics
Endometriosis - immunology
Endometriosis - pathology
Endometrium - immunology
Endometrium - pathology
eutopic endometrium
Female
Humans
Immunology
RNA-Seq
Single-Cell Analysis
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Summary: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.
ISSN:1664-3224
1664-3224
DOI:10.3389/fimmu.2021.788315