Spatial transcriptomic analysis identifies epithelium-macrophage crosstalk in endometriotic lesions

Summary: The mechanisms underlying the pathophysiology of endometriosis, characterized by the presence of endometrium-like tissue outside the uterus, remain poorly understood. This study aimed to identify cell type-specific gene expression changes in superficial peritoneal endometriotic lesions and...

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Main Authors: Gregory W. Burns, Zhen Fu, Erin L. Vegter, Zachary B. Madaj, Erin Greaves, Idhaliz Flores, Asgerally T. Fazleabas
Format: Article
Language:English
Published: Elsevier 2025-02-01
Series:iScience
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Online Access:http://www.sciencedirect.com/science/article/pii/S2589004225000495
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author Gregory W. Burns
Zhen Fu
Erin L. Vegter
Zachary B. Madaj
Erin Greaves
Idhaliz Flores
Asgerally T. Fazleabas
author_facet Gregory W. Burns
Zhen Fu
Erin L. Vegter
Zachary B. Madaj
Erin Greaves
Idhaliz Flores
Asgerally T. Fazleabas
author_sort Gregory W. Burns
collection DOAJ
description Summary: The mechanisms underlying the pathophysiology of endometriosis, characterized by the presence of endometrium-like tissue outside the uterus, remain poorly understood. This study aimed to identify cell type-specific gene expression changes in superficial peritoneal endometriotic lesions and elucidate the crosstalk among the stroma, epithelium, and macrophages compared to patient-matched eutopic endometrium. Surprisingly, comparison between lesions and eutopic endometrium revealed transcriptional similarities, indicating minimal alterations in the sub-epithelial stroma and epithelium of lesions. Spatial transcriptomics highlighted increased signaling between the lesion epithelium and macrophages, emphasizing the role of the epithelium in driving lesion inflammation. We propose that the superficial endometriotic lesion epithelium orchestrates inflammatory signaling and promotes a pro-repair phenotype in macrophages, providing a new role for complement 3 in lesion pathobiology. This study underscores the significance of considering spatial context and cellular interactions in uncovering mechanisms governing disease in endometriotic lesions.
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spelling doaj-art-3f27547c1e414501b5d64939d9841cd92025-01-29T05:01:37ZengElsevieriScience2589-00422025-02-01282111790Spatial transcriptomic analysis identifies epithelium-macrophage crosstalk in endometriotic lesionsGregory W. Burns0Zhen Fu1Erin L. Vegter2Zachary B. Madaj3Erin Greaves4Idhaliz Flores5Asgerally T. Fazleabas6Department of Obstetrics, Gynecology and Reproductive Biology, Michigan State University, Grand Rapids, MI 49503, USABioinformatics and Biostatistics, Van Andel Institute, Grand Rapids, MI 49503, USADepartment of Obstetrics, Gynecology and Reproductive Biology, Michigan State University, Grand Rapids, MI 49503, USABioinformatics and Biostatistics, Van Andel Institute, Grand Rapids, MI 49503, USADivision of Biomedical Sciences, Warwick Medical School, University of Warwick, Coventry CV4 7AL, UK; Centre for Early Life, University of Warwick, Coventry CV4 7AL, UKDepartment of Basic Sciences, Ponce Health Sciences University, Ponce, PR 00716, USA; Department of Obstetrics & Gynecology, Ponce Health Sciences University, Ponce, PR 00716, USADepartment of Obstetrics, Gynecology and Reproductive Biology, Michigan State University, Grand Rapids, MI 49503, USA; Corresponding authorSummary: The mechanisms underlying the pathophysiology of endometriosis, characterized by the presence of endometrium-like tissue outside the uterus, remain poorly understood. This study aimed to identify cell type-specific gene expression changes in superficial peritoneal endometriotic lesions and elucidate the crosstalk among the stroma, epithelium, and macrophages compared to patient-matched eutopic endometrium. Surprisingly, comparison between lesions and eutopic endometrium revealed transcriptional similarities, indicating minimal alterations in the sub-epithelial stroma and epithelium of lesions. Spatial transcriptomics highlighted increased signaling between the lesion epithelium and macrophages, emphasizing the role of the epithelium in driving lesion inflammation. We propose that the superficial endometriotic lesion epithelium orchestrates inflammatory signaling and promotes a pro-repair phenotype in macrophages, providing a new role for complement 3 in lesion pathobiology. This study underscores the significance of considering spatial context and cellular interactions in uncovering mechanisms governing disease in endometriotic lesions.http://www.sciencedirect.com/science/article/pii/S2589004225000495reproductive medicineintegrative aspects of cell biologyorganizational aspects of cell biologytranscriptomics
spellingShingle Gregory W. Burns
Zhen Fu
Erin L. Vegter
Zachary B. Madaj
Erin Greaves
Idhaliz Flores
Asgerally T. Fazleabas
Spatial transcriptomic analysis identifies epithelium-macrophage crosstalk in endometriotic lesions
iScience
reproductive medicine
integrative aspects of cell biology
organizational aspects of cell biology
transcriptomics
title Spatial transcriptomic analysis identifies epithelium-macrophage crosstalk in endometriotic lesions
title_full Spatial transcriptomic analysis identifies epithelium-macrophage crosstalk in endometriotic lesions
title_fullStr Spatial transcriptomic analysis identifies epithelium-macrophage crosstalk in endometriotic lesions
title_full_unstemmed Spatial transcriptomic analysis identifies epithelium-macrophage crosstalk in endometriotic lesions
title_short Spatial transcriptomic analysis identifies epithelium-macrophage crosstalk in endometriotic lesions
title_sort spatial transcriptomic analysis identifies epithelium macrophage crosstalk in endometriotic lesions
topic reproductive medicine
integrative aspects of cell biology
organizational aspects of cell biology
transcriptomics
url http://www.sciencedirect.com/science/article/pii/S2589004225000495
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AT erinlvegter spatialtranscriptomicanalysisidentifiesepitheliummacrophagecrosstalkinendometrioticlesions
AT zacharybmadaj spatialtranscriptomicanalysisidentifiesepitheliummacrophagecrosstalkinendometrioticlesions
AT eringreaves spatialtranscriptomicanalysisidentifiesepitheliummacrophagecrosstalkinendometrioticlesions
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