Single cell analysis of endometriosis reveals a coordinated transcriptional program driving immunotolerance and angiogenesis across eutopic and ectopic tissues.

Single cell analysis of endometriosis reveals a coordinated transcriptional program driving immunotolerance and angiogenesis across eutopic and ectopic tissues. | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article Single cell analysis of endometriosis reveals a coordinated transcriptional program driving immunotolerance and angiogenesis across eutopic and ectopic tissues. Elise Courtois, Yuliana Tan, William Flynn, Santosh Sivajothi, and 5 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-745435/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 21 Jul, 2022 Read the published version in Nature Cell Biology → Version 1 posted You are reading this latest preprint version Abstract Endometriosis is characterized by growth of endometrial-like tissue outside of the uterus affecting many women in their reproductive age, causing years of pelvic pain and potential infertility. Its pathophysiology remains largely unknown, limiting diagnosis and treatment. We characterized peritoneal and ovarian lesions at single-cell transcriptome resolution and compared to matched eutopic endometrium, control endometrium, and organoids derived from these tissues, generating data on over 100,000 cells across 12 individuals. We spatially localized many of the cell types using imaging mass cytometry. We identify a perivascular mural cell unique to the peritoneal lesions with dual roles in angiogenesis promotion and immune cell trafficking. We define an immunotolerant peritoneal niche, fundamental differences in eutopic endometrium and between lesions microenvironments, and a novel progenitor-like epithelial cell subpopulation. Altogether, this study provides a holistic view of the endometriosis microenvironment representing the first comprehensive cell atlas of the disease, essential information for advancing therapeutics and diagnostics. Immunology Endocrinology & Metabolism Medical Genetics endometriosis perivascular mural cell microenvironment Full Text Additional Declarations There is NO Competing Interest. Supplementary Files 02.markers.xlsx 03.DEGscRNAseqvsbulkRNAseq.xlsx 04.DEGbetweensampletypewithineachsubpopulation.xlsx 05.GSEA.xlsx 06.ListofAntibodyusedforscRNAseqhashtagingandIMC.xlsx Supplementalinformations.pdf Cite Share Download PDF Status: Published Journal Publication published 21 Jul, 2022 Read the published version in Nature Cell Biology → Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-745435","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":44297759,"identity":"e66fe65e-1402-468b-8fcf-4348d59c5278","order_by":0,"name":"Elise Courtois","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA8klEQVRIie3Rv2qDQBzA8d/xA7OEunoUzCucuBb7KspBnyHjBUEX6ZzH6CMoDl2uuhZclLyAkEXCDTW01WS42DHQ+y53N3y4fwAm0z22ImJehPCEywQngmfy8hdyPSuXhY0Y9z0ELmvqom1VvbL3ITlsT3pCY5LQPXCfVRxZlDToyBy9j1c9YSVJcA159CbRciLRILwLi+4yPXkuSXxUvyRUFW5KuE3Y+GKPMBErR3beRQx64owHoxnjPpXoj3fh6Mki9nZCT+w0PfTDNnAfJOm6QQXc/eRFJ5Se/BxvnnKA8XNJskQuCr6HxV1MJpPpH/UF3zVNUhfXHlcAAAAASUVORK5CYII=","orcid":"https://orcid.org/0000-0002-8749-2719","institution":"Jackson Lab for Genomic Medicine","correspondingAuthor":true,"prefix":"","firstName":"Elise","middleName":"","lastName":"Courtois","suffix":""},{"id":44297760,"identity":"d2a7f4cb-87aa-4d64-b62b-e7b7508d6c10","order_by":1,"name":"Yuliana Tan","email":"","orcid":"https://orcid.org/0000-0002-5923-2215","institution":"The Jacksopn Laboratory for Genomic Medicine","correspondingAuthor":false,"prefix":"","firstName":"Yuliana","middleName":"","lastName":"Tan","suffix":""},{"id":44297761,"identity":"cc4fc5c5-2974-4cac-95ef-6e9bbe8d85e6","order_by":2,"name":"William Flynn","email":"","orcid":"https://orcid.org/0000-0001-6533-0340","institution":"The Jackson Laboratory","correspondingAuthor":false,"prefix":"","firstName":"William","middleName":"","lastName":"Flynn","suffix":""},{"id":44297762,"identity":"6b1e51dd-37e9-4be3-94fa-43f30d8d3a8c","order_by":3,"name":"Santosh Sivajothi","email":"","orcid":"","institution":"The Jackson Laboratory for Genomic Medicine","correspondingAuthor":false,"prefix":"","firstName":"Santosh","middleName":"","lastName":"Sivajothi","suffix":""},{"id":44297763,"identity":"83fe57a5-d058-46ee-bac9-d625f439921a","order_by":4,"name":"Diane Luo","email":"","orcid":"","institution":"The Jackson Laboratory for Genomic Medicine","correspondingAuthor":false,"prefix":"","firstName":"Diane","middleName":"","lastName":"Luo","suffix":""},{"id":44297764,"identity":"645b4787-0d8d-414e-b484-e48bdf2847e4","order_by":5,"name":"Suleyman Bozal","email":"","orcid":"","institution":"The Jackson Laboratory for Genomic Medicine","correspondingAuthor":false,"prefix":"","firstName":"Suleyman","middleName":"","lastName":"Bozal","suffix":""},{"id":44297765,"identity":"ad9cb34d-8f6a-41bb-a5a0-fe85a23690d0","order_by":6,"name":"Anthony Luciano","email":"","orcid":"","institution":"University of Connecticut","correspondingAuthor":false,"prefix":"","firstName":"Anthony","middleName":"","lastName":"Luciano","suffix":""},{"id":44297766,"identity":"177568c1-2c12-4535-bf84-508a8fd7ecdb","order_by":7,"name":"Paul Robson","email":"","orcid":"https://orcid.org/0000-0002-0191-3958","institution":"The Jackson Laboratory for Genomic Medicine","correspondingAuthor":false,"prefix":"","firstName":"Paul","middleName":"","lastName":"Robson","suffix":""},{"id":44297767,"identity":"07507324-931f-49c9-a8f9-76b6a99fb6dc","order_by":8,"name":"Danielle Luciano","email":"","orcid":"","institution":"University of Connecticut","correspondingAuthor":false,"prefix":"","firstName":"Danielle","middleName":"","lastName":"Luciano","suffix":""}],"badges":[],"createdAt":"2021-07-23 23:10:31","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-745435/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-745435/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1038/s41556-022-00961-5","type":"published","date":"2022-07-21T04:00:00+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":24422164,"identity":"241a8c2d-ef3a-4c53-b097-bfe75eacccdc","added_by":"auto","created_at":"2022-07-27 19:21:39","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":14214592,"visible":true,"origin":"","legend":"","description":"","filename":"Tanetal2021final20210723.pdf","url":"https://assets-eu.researchsquare.com/files/rs-745435/v1_covered.pdf"},{"id":13666336,"identity":"a8ec8f3d-597d-4f39-9cf9-50c91e406ada","added_by":"auto","created_at":"2021-09-17 10:48:09","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":14209061,"visible":true,"origin":"","legend":"","description":"","filename":"Tanetal2021final20210723.pdf","url":"https://assets-eu.researchsquare.com/files/rs-745435/v1_covered.pdf"},{"id":12261759,"identity":"bd2641ab-aa7c-478b-93ee-dd90b8e050d3","added_by":"auto","created_at":"2021-08-09 19:45:22","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":14205459,"visible":true,"origin":"","legend":"","description":"","filename":"Tanetal2021final20210723.pdf","url":"https://assets-eu.researchsquare.com/files/rs-745435/v1_covered.pdf"},{"id":12261667,"identity":"6540b112-5263-48bd-a416-91257c510a36","added_by":"auto","created_at":"2021-08-09 19:44:41","extension":"xlsx","order_by":2,"title":"","display":"","copyAsset":false,"role":"supplement","size":397443,"visible":true,"origin":"","legend":"","description":"","filename":"02.markers.xlsx","url":"https://assets-eu.researchsquare.com/files/rs-745435/v1/1cc5b850d81dc16f1112b308.xlsx"},{"id":12261615,"identity":"5c54c0ba-68d2-418a-bb61-36c16c1fc75d","added_by":"auto","created_at":"2021-08-09 19:41:41","extension":"xlsx","order_by":3,"title":"","display":"","copyAsset":false,"role":"supplement","size":930828,"visible":true,"origin":"","legend":"","description":"","filename":"03.DEGscRNAseqvsbulkRNAseq.xlsx","url":"https://assets-eu.researchsquare.com/files/rs-745435/v1/726c4e44c003fdfbacb36fde.xlsx"},{"id":12261616,"identity":"de7d8048-6277-427b-a646-09f738376af4","added_by":"auto","created_at":"2021-08-09 19:41:41","extension":"xlsx","order_by":4,"title":"","display":"","copyAsset":false,"role":"supplement","size":5121546,"visible":true,"origin":"","legend":"","description":"","filename":"04.DEGbetweensampletypewithineachsubpopulation.xlsx","url":"https://assets-eu.researchsquare.com/files/rs-745435/v1/d51e7d356da928085fcb7d1e.xlsx"},{"id":12261613,"identity":"9678c5c3-17b5-462b-9964-a84d63537578","added_by":"auto","created_at":"2021-08-09 19:41:41","extension":"xlsx","order_by":5,"title":"","display":"","copyAsset":false,"role":"supplement","size":1121366,"visible":true,"origin":"","legend":"","description":"","filename":"05.GSEA.xlsx","url":"https://assets-eu.researchsquare.com/files/rs-745435/v1/a71bc48a422f39de35536ab0.xlsx"},{"id":12261612,"identity":"3b5cbf1c-268c-472e-b133-074d4b6ebd19","added_by":"auto","created_at":"2021-08-09 19:41:41","extension":"xlsx","order_by":6,"title":"","display":"","copyAsset":false,"role":"supplement","size":11815,"visible":true,"origin":"","legend":"","description":"","filename":"06.ListofAntibodyusedforscRNAseqhashtagingandIMC.xlsx","url":"https://assets-eu.researchsquare.com/files/rs-745435/v1/2f9a252bfe74f9577fc9edaa.xlsx"},{"id":12261617,"identity":"90bb5294-208f-4742-bbdf-a4c49c6a1f76","added_by":"auto","created_at":"2021-08-09 19:41:41","extension":"pdf","order_by":7,"title":"","display":"","copyAsset":false,"role":"supplement","size":12057819,"visible":true,"origin":"","legend":"","description":"","filename":"Supplementalinformations.pdf","url":"https://assets-eu.researchsquare.com/files/rs-745435/v1/0d53933b0300ecbfeba44434.pdf"}],"financialInterests":"There is \u003cb\u003eNO\u003c/b\u003e Competing Interest.","formattedTitle":"Single cell analysis of endometriosis reveals a coordinated transcriptional program driving immunotolerance and angiogenesis across eutopic and ectopic tissues.","fulltext":[{"header":"Full Text","content":"This preprint is available for \u003ca href='/article/rs-745435/latest.pdf' target='_blank'\u003edownload as a PDF\u003c/a\u003e."}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":false,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":true,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"nature-portfolio","isNatureJournal":true,"hasQc":false,"allowDirectSubmit":false,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"","title":"Nature Portfolio","twitterHandle":"","acdcEnabled":false,"dfaEnabled":false,"editorialSystem":"ejp","reportingPortfolio":"","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"endometriosis, perivascular mural cell, microenvironment","lastPublishedDoi":"10.21203/rs.3.rs-745435/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-745435/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"Endometriosis is characterized by growth of endometrial-like tissue outside of the uterus affecting many women in their reproductive age, causing years of pelvic pain and potential infertility. Its pathophysiology remains largely unknown, limiting diagnosis and treatment. We characterized peritoneal and ovarian lesions at single-cell transcriptome resolution and compared to matched eutopic endometrium, control endometrium, and organoids derived from these tissues, generating data on over 100,000 cells across 12 individuals. We spatially localized many of the cell types using imaging mass cytometry. We identify a perivascular mural cell unique to the peritoneal lesions with dual roles in angiogenesis promotion and immune cell trafficking. We define an immunotolerant peritoneal niche, fundamental differences in eutopic endometrium and between lesions microenvironments, and a novel progenitor-like epithelial cell subpopulation. Altogether, this study provides a holistic view of the endometriosis microenvironment representing the first comprehensive cell atlas of the disease, essential information for advancing therapeutics and diagnostics.","manuscriptTitle":"Single cell analysis of endometriosis reveals a coordinated transcriptional program driving immunotolerance and angiogenesis across eutopic and ectopic tissues.","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2021-08-09 19:41:39","doi":"10.21203/rs.3.rs-745435/v1","editorialEvents":[],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"nature-cell-biology","isNatureJournal":true,"hasQc":false,"allowDirectSubmit":false,"externalIdentity":"ncb","sideBox":"Learn more about [Nature Cell Biology](http://www.nature.com/ncb/)","snPcode":"","submissionUrl":"","title":"Nature Cell Biology","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"ejp","reportingPortfolio":"Nature Research","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"ef2d8e41-f5a7-491e-a82d-977e73337c98","owner":[],"postedDate":"August 9th, 2021","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[{"id":6331721,"name":"Immunology"},{"id":6331722,"name":"Endocrinology \u0026 Metabolism"},{"id":6331723,"name":"Medical Genetics"}],"tags":[],"updatedAt":"2022-07-27T19:21:00+00:00","versionOfRecord":{"articleIdentity":"rs-745435","link":"https://doi.org/10.1038/s41556-022-00961-5","journal":{"identity":"nature-cell-biology","isVorOnly":false,"title":"Nature Cell Biology"},"publishedOn":"2022-07-21 04:00:00","publishedOnDateReadable":"July 21st, 2022"},"versionCreatedAt":"2021-08-09 19:41:39","video":"","vorDoi":"10.1038/s41556-022-00961-5","vorDoiUrl":"https://doi.org/10.1038/s41556-022-00961-5","workflowStages":[]},"version":"v1","identity":"rs-745435","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-745435","identity":"rs-745435","version":["v1"]},"buildId":"WvIrzKhiLBfengagbw6Ux","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}