The single-cell transcriptional landscape of the axolotl | 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 The single-cell transcriptional landscape of the axolotl Fang Ye, Guodong Zhang, Weigao E, Haide Chen, Chengxuan Yu, Jiaqi Li, and 16 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-960203/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 22 Jul, 2022 Read the published version in Nature Communications → Version 1 posted You are reading this latest preprint version Abstract The Mexican axolotl (Ambystoma mexicanum) is a promising tetrapod model for regeneration and developmental studies. Remarkably, neotenic axolotls may undergo metamorphosis, during which their regeneration capacity and lifespan gradually decline. However, a system-level single-cell analysis of molecular characteristics in neotenic and metamorphosed axolotls is still lacking. Here, we developed a single-cell RNA-seq method based on combinatorial hybridization to generate a tissue-based transcriptomic atlas of the adult axolotl. We performed gene expression profiling of over 1 million single cells across 19 tissues to construct the first adult axolotl cell atlas. Comparison of single-cell transcriptomes between the tissues of neotenic and metamorphosed axolotls revealed the heterogeneity of structural cells in different tissues and established their regulatory network. Furthermore, we described dynamic gene expression patterns during limb development in neotenic axolotls. These data serve as a resource to explore the molecular identity of the axolotl as well as its metamorphosis. Evolutionary Biology Evolutionary Developmental Biology axolotl transcriptomics gene expression metamorphosis Full Text Additional Declarations There is NO Competing Interest. Supplementary Files TableS1CHseqoligos.xlsx Supplementary table1 Supplementaryfiguresandfigureslegends.pdf TableS2RNAreadsGenesinFigure1C.xlsx Supplementary table2 TableS4GeneregulatorynetworksparametersofNodesGenes.xlsx Supplementary table4 TableS3Differentiallyexpressedgenesinparenchymacells.xlsx Supplementary table3 Cite Share Download PDF Status: Published Journal Publication published 22 Jul, 2022 Read the published version in Nature Communications → 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-960203","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":56407426,"identity":"41490b96-fb9c-4da1-999d-a98900e84bd6","order_by":0,"name":"Fang Ye","email":"","orcid":"","institution":"Zhejiang University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Fang","middleName":"","lastName":"Ye","suffix":""},{"id":56407427,"identity":"db4744fd-7f2c-415d-bb62-1553fe95889e","order_by":1,"name":"Guodong Zhang","email":"","orcid":"","institution":"Zhejiang University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Guodong","middleName":"","lastName":"Zhang","suffix":""},{"id":56407428,"identity":"7efc247a-0f2c-40cf-b774-649a7cae6a76","order_by":2,"name":"Weigao E","email":"","orcid":"","institution":"Zhejiang University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Weigao","middleName":"","lastName":"E","suffix":""},{"id":56407429,"identity":"9df83d93-b973-484f-bf5a-995c78891069","order_by":3,"name":"Haide Chen","email":"","orcid":"","institution":"Zhejiang University School of Medicine","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Haide","middleName":"","lastName":"Chen","suffix":""},{"id":56407430,"identity":"20b1c5f9-5637-4198-b977-6db5eb00efcd","order_by":4,"name":"Chengxuan Yu","email":"","orcid":"","institution":"Zhejiang University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Chengxuan","middleName":"","lastName":"Yu","suffix":""},{"id":56407431,"identity":"f1a3cd53-3462-45d7-ad65-8cc46624dd15","order_by":5,"name":"Jiaqi Li","email":"","orcid":"","institution":"Zhejiang University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Jiaqi","middleName":"","lastName":"Li","suffix":""},{"id":56407432,"identity":"90ff0b53-7d2a-4d97-a525-ab182fe478c9","order_by":6,"name":"Yuting Fu","email":"","orcid":"","institution":"Zhejiang University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Yuting","middleName":"","lastName":"Fu","suffix":""},{"id":56407433,"identity":"cab48408-e8b2-4230-a5dd-0f90cc731260","order_by":7,"name":"Zhongyi Sun","email":"","orcid":"","institution":"Zhejiang University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Zhongyi","middleName":"","lastName":"Sun","suffix":""},{"id":56407434,"identity":"eef909d2-e84a-4048-91c1-10c9a6a2d144","order_by":8,"name":"Lijiang Fei","email":"","orcid":"","institution":"Zhejiang University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Lijiang","middleName":"","lastName":"Fei","suffix":""},{"id":56407435,"identity":"121f901e-7b0c-4073-bd3b-4cfe508ee527","order_by":9,"name":"Qile Guo","email":"","orcid":"","institution":"Zhejiang University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Qile","middleName":"","lastName":"Guo","suffix":""},{"id":56407436,"identity":"1088b1f7-4f3e-45d6-b6da-2fbc5f61af80","order_by":10,"name":"Lei Yang","email":"","orcid":"","institution":"Zhejiang University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Lei","middleName":"","lastName":"Yang","suffix":""},{"id":56407437,"identity":"4faa1525-76b3-40a9-a949-951bd2e2d123","order_by":11,"name":"Jingjing Wang","email":"","orcid":"","institution":"Zhejiang University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Jingjing","middleName":"","lastName":"Wang","suffix":""},{"id":56407438,"identity":"5fb9ef68-28e7-405d-a301-08bf95aea69d","order_by":12,"name":"Yanyu Xiao","email":"","orcid":"","institution":"Zhejiang University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Yanyu","middleName":"","lastName":"Xiao","suffix":""},{"id":56407439,"identity":"4489c143-1b41-48dd-83c0-4a10f74b26b6","order_by":13,"name":"Xinru Wang","email":"","orcid":"","institution":"Zhejiang University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Xinru","middleName":"","lastName":"Wang","suffix":""},{"id":56407440,"identity":"1625982a-6c78-4847-ba73-dacdf4235274","order_by":14,"name":"Peijing Zhang","email":"","orcid":"","institution":"Zhejiang University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Peijing","middleName":"","lastName":"Zhang","suffix":""},{"id":56407441,"identity":"6014725a-b81c-42d8-85ff-f17d7824431d","order_by":15,"name":"Li Feng Ma","email":"","orcid":"","institution":"","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Li","middleName":"Feng","lastName":"Ma","suffix":""},{"id":56407442,"identity":"9f188f0f-0372-4cd0-afe6-87d938e62264","order_by":16,"name":"Sulei Fu","email":"","orcid":"","institution":"","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Sulei","middleName":"","lastName":"Fu","suffix":""},{"id":56407443,"identity":"0635fa52-6206-4b52-8f9f-16b880c1da74","order_by":17,"name":"Jifeng Fei","email":"","orcid":"","institution":"Guangdong Provincial People's Hospital","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Jifeng","middleName":"","lastName":"Fei","suffix":""},{"id":56407444,"identity":"95ecdd1d-0f18-4c4c-84c9-357eb66e892e","order_by":18,"name":"Dapeng Ge","email":"","orcid":"","institution":"Zhejiang University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Dapeng","middleName":"","lastName":"Ge","suffix":""},{"id":56407445,"identity":"6381f0ec-abb7-4ee1-a1a5-ed7e9c3e4b02","order_by":19,"name":"Suhong Xu","email":"","orcid":"https://orcid.org/0000-0002-4079-340X","institution":"Zhejiang University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Suhong","middleName":"","lastName":"Xu","suffix":""},{"id":56407446,"identity":"3f3c4859-0e33-44bc-8b6c-6558f5a79709","order_by":20,"name":"Xiaoping Han","email":"","orcid":"https://orcid.org/0000-0003-3201-7635","institution":"Zhejiang University School of Medicine","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Xiaoping","middleName":"","lastName":"Han","suffix":""},{"id":56407447,"identity":"f99a57d5-5349-4649-8778-7860862b3c7f","order_by":21,"name":"Guoji Guo","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAtUlEQVRIiWNgGAWjYHCCBIYHDAfk2NjbD5CgJYHhgDEfz5kEkuw5kDhPwsGAONXy/gseMCTU3ElvkwDq/FGxjbAWwxsPgA479iy3TbrxAGPPmdtEaJlxAKiF7XBum8yBBGbGNqK1/DucziaRYECcFnn+hgSGxLbDCcRrMQD5OrHvmWEbMJAPEuUX+X5gdHz4dkdevr394IMfFcTYciMn/QeMc4CwerAtx4lTOApGwSgYBSMYAAAqskJtfGB92AAAAABJRU5ErkJggg==","orcid":"","institution":"Zhejiang University","correspondingAuthor":true,"submittingAuthor":false,"prefix":"","firstName":"Guoji","middleName":"","lastName":"Guo","suffix":""}],"badges":[],"createdAt":"2021-10-08 09:21:10","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-960203/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-960203/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1038/s41467-022-31879-z","type":"published","date":"2022-07-22T04:00:00+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":24233556,"identity":"990a8ed8-aeb0-46e8-8d77-2569575f3604","added_by":"auto","created_at":"2022-07-23 11:25:03","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":13851492,"visible":true,"origin":"","legend":"","description":"","filename":"ManuscriptFigurelegendsFigures.pdf","url":"https://assets-eu.researchsquare.com/files/rs-960203/v1_covered.pdf"},{"id":14494554,"identity":"200de44a-fd7a-4c5a-94bb-c35e87a58114","added_by":"auto","created_at":"2021-10-13 15:45:49","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":13846250,"visible":true,"origin":"","legend":"","description":"","filename":"ManuscriptFigurelegendsFigures.pdf","url":"https://assets-eu.researchsquare.com/files/rs-960203/v1_covered.pdf"},{"id":14494402,"identity":"0199a12d-89bb-407b-92b9-102d8e38289b","added_by":"auto","created_at":"2021-10-13 15:42:31","extension":"xlsx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":44500,"visible":true,"origin":"","legend":"Supplementary table1","description":"","filename":"TableS1CHseqoligos.xlsx","url":"https://assets-eu.researchsquare.com/files/rs-960203/v1/d4cf2da6893f6ccec1ecc6de.xlsx"},{"id":14494406,"identity":"b2cc5247-3bc3-421d-8c7c-30c0ad5730fe","added_by":"auto","created_at":"2021-10-13 15:42:32","extension":"pdf","order_by":2,"title":"","display":"","copyAsset":false,"role":"supplement","size":6384634,"visible":true,"origin":"","legend":"","description":"","filename":"Supplementaryfiguresandfigureslegends.pdf","url":"https://assets-eu.researchsquare.com/files/rs-960203/v1/59c43d1be52dc613b6664fb4.pdf"},{"id":14494404,"identity":"a9710d30-03b0-45cb-a16e-7c9c50b10aeb","added_by":"auto","created_at":"2021-10-13 15:42:32","extension":"xlsx","order_by":3,"title":"","display":"","copyAsset":false,"role":"supplement","size":154348,"visible":true,"origin":"","legend":"Supplementary table2","description":"","filename":"TableS2RNAreadsGenesinFigure1C.xlsx","url":"https://assets-eu.researchsquare.com/files/rs-960203/v1/5ad4dc0e5346d3c596fdce8b.xlsx"},{"id":14494527,"identity":"98f9973d-192d-4ba4-b79f-9f049eaa54b3","added_by":"auto","created_at":"2021-10-13 15:45:32","extension":"xlsx","order_by":4,"title":"","display":"","copyAsset":false,"role":"supplement","size":178467,"visible":true,"origin":"","legend":"Supplementary table4","description":"","filename":"TableS4GeneregulatorynetworksparametersofNodesGenes.xlsx","url":"https://assets-eu.researchsquare.com/files/rs-960203/v1/3e0da294701b9f7fb03d65eb.xlsx"},{"id":14494403,"identity":"4df6c17d-0012-41f3-90f9-9756c08cd930","added_by":"auto","created_at":"2021-10-13 15:42:31","extension":"xlsx","order_by":5,"title":"","display":"","copyAsset":false,"role":"supplement","size":95306,"visible":true,"origin":"","legend":"Supplementary table3","description":"","filename":"TableS3Differentiallyexpressedgenesinparenchymacells.xlsx","url":"https://assets-eu.researchsquare.com/files/rs-960203/v1/5464da8d27163c2a39cc9c81.xlsx"}],"financialInterests":"There is \u003cb\u003eNO\u003c/b\u003e Competing Interest.","formattedTitle":"The single-cell transcriptional landscape of the axolotl","fulltext":[{"header":"Full Text","content":"This preprint is available for \u003ca href='/article/rs-960203/latest.pdf' target='_blank'\u003edownload as a PDF\u003c/a\u003e."}],"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":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":"axolotl, transcriptomics, gene expression, metamorphosis","lastPublishedDoi":"10.21203/rs.3.rs-960203/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-960203/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"The Mexican axolotl (Ambystoma mexicanum) is a promising tetrapod model for regeneration and developmental studies. Remarkably, neotenic axolotls may undergo metamorphosis, during which their regeneration capacity and lifespan gradually decline. However, a system-level single-cell analysis of molecular characteristics in neotenic and metamorphosed axolotls is still lacking. Here, we developed a single-cell RNA-seq method based on combinatorial hybridization to generate a tissue-based transcriptomic atlas of the adult axolotl. We performed gene expression profiling of over 1 million single cells across 19 tissues to construct the first adult axolotl cell atlas. Comparison of single-cell transcriptomes between the tissues of neotenic and metamorphosed axolotls revealed the heterogeneity of structural cells in different tissues and established their regulatory network. Furthermore, we described dynamic gene expression patterns during limb development in neotenic axolotls. These data serve as a resource to explore the molecular identity of the axolotl as well as its metamorphosis.","manuscriptTitle":"The single-cell transcriptional landscape of the axolotl","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2021-10-13 15:42:30","doi":"10.21203/rs.3.rs-960203/v1","editorialEvents":[],"status":"published","journal":{"display":true,"email":"
[email protected]","identity":"nature-communications","isNatureJournal":true,"hasQc":false,"allowDirectSubmit":false,"externalIdentity":"NCOMMS","sideBox":"Learn more about [Nature Communications](http://www.nature.com/ncomms/)","snPcode":"","submissionUrl":"https://mts-ncomms.nature.com/","title":"Nature Communications","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"ejp","reportingPortfolio":"Nature Communications","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"b918c6e5-220a-4bc2-9d81-52db149c386d","owner":[],"postedDate":"October 13th, 2021","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[{"id":7837685,"name":"Evolutionary Biology"},{"id":7837686,"name":"Evolutionary Developmental Biology"}],"tags":[],"updatedAt":"2022-07-23T11:24:40+00:00","versionOfRecord":{"articleIdentity":"rs-960203","link":"https://doi.org/10.1038/s41467-022-31879-z","journal":{"identity":"nature-communications","isVorOnly":false,"title":"Nature Communications"},"publishedOn":"2022-07-22 04:00:00","publishedOnDateReadable":"July 22nd, 2022"},"versionCreatedAt":"2021-10-13 15:42:30","video":"","vorDoi":"10.1038/s41467-022-31879-z","vorDoiUrl":"https://doi.org/10.1038/s41467-022-31879-z","workflowStages":[]},"version":"v1","identity":"rs-960203","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-960203","identity":"rs-960203","version":["v1"]},"buildId":"cBFmMYwuxLRRLfASyISRj","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}
Text is read by the "Ask this paper" AI Q&A widget below.
Extraction quality varies by source — PMC NXML preserves structure
cleanly, OA-HTML may include some navigation residue, and OA-PDF can
have broken hyphenation. The publisher copy
(via DOI)
is the canonical version.