Integrated multi-omics single cell atlas of the human retina

Integrated multi-omics single cell atlas of the human retina | 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 Integrated multi-omics single cell atlas of the human retina Rui Chen, Jin Li, Jun Wang, Ignacio Ibarra, Xuesen Cheng, Malte Luecken, and 16 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-3471275/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 23 Jan, 2026 Read the published version in Nature Genetics → Version 1 posted You are reading this latest preprint version Abstract Single-cell sequencing has revolutionized the scale and resolution of molecular profiling of tissues and organs. Here, we present an integrated multimodal reference atlas of the most accessible portion of the mammalian central nervous system, the retina. We compiled around 2.4 million cells from 55 donors, including 1.4 million unpublished data points, to create a comprehensive human retina cell atlas (HRCA) of transcriptome and chromatin accessibility, unveiling over 110 types. Engaging the retina community, we annotated each cluster, refined the Cell Ontology for the retina, identified distinct marker genes, and characterized cis-regulatory elements and gene regulatory networks (GRNs) for these cell types. Our analysis uncovered intriguing differences in transcriptome, chromatin, and GRNs across cell types. In addition, we modeled changes in gene expression and chromatin openness across gender and age. This integrated atlas also enabled the fine-mapping of GWAS and eQTL variants. Accessible through interactive browsers, this multimodal cross-donor and cross-lab HRCA, can facilitate a better understanding of retinal function and pathology. Biological sciences/Molecular biology/Transcriptomics Biological sciences/Genetics/Genetic association study/Genome-wide association studies Biological sciences/Genetics/Sequencing Full Text Additional Declarations Yes there is potential Competing Interest. F.J.T. consults for Immunai Inc., CytoReason Ltd, Cellarity Inc and Omniscope Ltd, and owns interests in Dermagnostix GmbH and Cellarity Inc. Other authors declare no competing interests. Supplementary Files HumanRetinaAtlassupplementaryfigures.pdf Supplementary Figure HumanRetinaAtlassupplementarynote.pdf Supplementary Note SupplementaryTable1.xlsx Supplementary Table 1 SupplementaryTable2.xlsx Supplementary Table 2 SupplementaryTable3.xlsx Supplementary Table 3 SupplementaryTable4.xlsx Supplementary Table 4 SupplementaryTable5.xlsx Supplementary Table 5 SupplementaryTable6.xlsx Supplementary Table 6 SupplementaryTable7.xlsx Supplementary Table 7 SupplementaryTable8.xlsx Supplementary Table 8 SupplementaryTable9.xlsx Supplementary Table 9 SupplementaryTable10.xlsx Supplementary Table 10 SupplementaryTable11.xlsx Supplementary Table 11 SupplementaryTable12.xlsx Supplementary Table 12 SupplementaryTable13.xlsx Supplementary Table 13 SupplementaryTable14.xlsx Supplementary Table 14 SupplementaryTable15.xlsx Supplementary Table 15 SupplementaryTable16.xlsx Supplementary Table 16 SupplementaryTable17.xlsx Supplementary Table 17 SupplementaryTable18.xls Supplementary Table 18 SupplementaryTable19.xlsx Supplementary Table 19 SupplementaryTable20.xlsx Supplementary Table 20 SupplementaryTable21.xlsx Supplementary Table 21 Cite Share Download PDF Status: Published Journal Publication published 23 Jan, 2026 Read the published version in Nature Genetics → 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. 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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-3471275","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":249834859,"identity":"0f5d8a97-2926-41f7-bcfd-03333b8b64d0","order_by":0,"name":"Rui 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Other authors declare no competing interests.","formattedTitle":"Integrated multi-omics single cell atlas of the human retina","fulltext":[],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":false,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":true,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":true,"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":"","lastPublishedDoi":"10.21203/rs.3.rs-3471275/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-3471275/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"Single-cell sequencing has revolutionized the scale and resolution of molecular profiling of tissues and organs. Here, we present an integrated multimodal reference atlas of the most accessible portion of the mammalian central nervous system, the retina. We compiled around 2.4 million cells from 55 donors, including 1.4 million unpublished data points, to create a comprehensive human retina cell atlas (HRCA) of transcriptome and chromatin accessibility, unveiling over 110 types. Engaging the retina community, we annotated each cluster, refined the Cell Ontology for the retina, identified distinct marker genes, and characterized cis-regulatory elements and gene regulatory networks (GRNs) for these cell types. Our analysis uncovered intriguing differences in transcriptome, chromatin, and GRNs across cell types. In addition, we modeled changes in gene expression and chromatin openness across gender and age. This integrated atlas also enabled the fine-mapping of GWAS and eQTL variants. Accessible through interactive browsers, this multimodal cross-donor and cross-lab HRCA, can facilitate a better understanding of retinal function and pathology.","manuscriptTitle":"Integrated multi-omics single cell atlas of the human retina","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2023-11-17 04:18:24","doi":"10.21203/rs.3.rs-3471275/v1","editorialEvents":[],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"nature-genetics","isNatureJournal":true,"hasQc":false,"allowDirectSubmit":false,"externalIdentity":"ng","sideBox":"Learn more about [Nature Genetics](http://www.nature.com/ng/)","snPcode":"","submissionUrl":"","title":"Nature Genetics","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"ejp","reportingPortfolio":"Nature Research","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"0a0ed228-d731-4ad0-a300-94e8bfd66b13","owner":[],"postedDate":"November 17th, 2023","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[{"id":26373139,"name":"Biological sciences/Molecular biology/Transcriptomics"},{"id":26373140,"name":"Biological sciences/Genetics/Genetic association study/Genome-wide association studies"},{"id":26373141,"name":"Biological sciences/Genetics/Sequencing"}],"tags":[],"updatedAt":"2026-01-27T09:45:00+00:00","versionOfRecord":{"articleIdentity":"rs-3471275","link":"https://doi.org/10.1038/s41588-025-02454-1","journal":{"identity":"nature-genetics","isVorOnly":false,"title":"Nature Genetics"},"publishedOn":"2026-01-23 05:00:00","publishedOnDateReadable":"January 23rd, 2026"},"versionCreatedAt":"2023-11-17 04:18:24","video":"","vorDoi":"10.1038/s41588-025-02454-1","vorDoiUrl":"https://doi.org/10.1038/s41588-025-02454-1","workflowStages":[]},"version":"v1","identity":"rs-3471275","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-3471275","identity":"rs-3471275","version":["v1"]},"buildId":"-HB7Z8yhvgn0wM9Nzuekk","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}