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...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-01-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2021.788315/full |
| _version_ | 1831704386697428992 |
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| author | 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 Marina Sirota |
| author_facet | 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 Marina Sirota |
| author_sort | Daniel G. Bunis |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-20T15:57:21Z |
| format | Article |
| id | doaj.art-4733fe4718cf4973b6070d00bd323c92 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-20T15:57:21Z |
| publishDate | 2022-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-4733fe4718cf4973b6070d00bd323c922022-12-21T19:34:25ZengFrontiers Media S.A.Frontiers in Immunology1664-32242022-01-011210.3389/fimmu.2021.788315788315Whole-Tissue Deconvolution and scRNAseq Analysis Identify Altered Endometrial Cellular Compositions and Functionality Associated With EndometriosisDaniel G. Bunis0Wanxin Wang1Júlia Vallvé-Juanico2Sahar Houshdaran3Sushmita Sen4Isam Ben Soltane5Idit Kosti6Kim Chi Vo7Juan C. Irwin8Linda C. Giudice9Marina Sirota10Marina Sirota11Bakar Computational Health Sciences Institute, University of California, San Francisco, San Francisco, CA, United StatesCenter for Reproductive Sciences, University of California, San Francisco, San Francisco, CA, United StatesCenter for Reproductive Sciences, University of California, San Francisco, San Francisco, CA, United StatesCenter for Reproductive Sciences, University of California, San Francisco, San Francisco, CA, United StatesCenter for Reproductive Sciences, University of California, San Francisco, San Francisco, CA, United StatesBakar Computational Health Sciences Institute, University of California, San Francisco, San Francisco, CA, United StatesBakar Computational Health Sciences Institute, University of California, San Francisco, San Francisco, CA, United StatesCenter for Reproductive Sciences, University of California, San Francisco, San Francisco, CA, United StatesCenter for Reproductive Sciences, University of California, San Francisco, San Francisco, CA, United StatesCenter for Reproductive Sciences, University of California, San Francisco, San Francisco, CA, United StatesBakar Computational Health Sciences Institute, University of California, San Francisco, San Francisco, CA, United StatesDepartment of Pediatrics, Division of Neonatology, University of California, San Francisco, San Francisco, CA, United StatesThe 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.https://www.frontiersin.org/articles/10.3389/fimmu.2021.788315/fullendometriosisdeconvolutionbulk tissue transcriptomicssingle-cell analysiseutopic endometrium |
| spellingShingle | 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 Marina Sirota Whole-Tissue Deconvolution and scRNAseq Analysis Identify Altered Endometrial Cellular Compositions and Functionality Associated With Endometriosis Frontiers in Immunology endometriosis deconvolution bulk tissue transcriptomics single-cell analysis eutopic endometrium |
| title | Whole-Tissue Deconvolution and scRNAseq Analysis Identify Altered Endometrial Cellular Compositions and Functionality Associated With Endometriosis |
| title_full | Whole-Tissue Deconvolution and scRNAseq Analysis Identify Altered Endometrial Cellular Compositions and Functionality Associated With Endometriosis |
| title_fullStr | Whole-Tissue Deconvolution and scRNAseq Analysis Identify Altered Endometrial Cellular Compositions and Functionality Associated With Endometriosis |
| title_full_unstemmed | Whole-Tissue Deconvolution and scRNAseq Analysis Identify Altered Endometrial Cellular Compositions and Functionality Associated With Endometriosis |
| title_short | Whole-Tissue Deconvolution and scRNAseq Analysis Identify Altered Endometrial Cellular Compositions and Functionality Associated With Endometriosis |
| title_sort | whole tissue deconvolution and scrnaseq analysis identify altered endometrial cellular compositions and functionality associated with endometriosis |
| topic | endometriosis deconvolution bulk tissue transcriptomics single-cell analysis eutopic endometrium |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2021.788315/full |
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