IK is essentially involved in ciliogenesis as an upstream regulator of oral-facial-digital syndrome ciliopathy gene,ofd1

IK is essentially involved in ciliogenesis as an upstream regulator of oral-facial-digital syndrome ciliopathy gene,ofd1 | 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 Research Article IK is essentially involved in ciliogenesis as an upstream regulator of oral-facial-digital syndrome ciliopathy gene,ofd1 Hye In Ka, Mina Cho, Seung-Hae Kwon, Se Hwan Mun, Sora Han, Min Jung Kim, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-2896500/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 28 Oct, 2023 Read the published version in Cell & Bioscience → Version 1 posted 4 You are reading this latest preprint version Abstract Background The cilia are microtubule-based organelles that protrude from the cell surface. Abnormalities in cilia result in various ciliopathies, including polycystic kidney disease (PKD), Bardet-Biedl syndrome (BBS), and oral-facial-digital syndrome type I (OFD1), which show genetic defects associated with cilia formation. Although an increasing number of human diseases is attributed to ciliary defects, the functions or regulatory mechanisms of several ciliopathy genes remain unclear. Because cilia are deep in vivo, studying ciliogenesis is challenging. Here, we demonstrate that IK is essential for ciliogenesis in vivo. Results In the absence of IK, zebrafish embryos showed various ciliopathy phenotypes, such as body curvature, abnormal otoliths, and cyst formation in the kidney. RNA sequencing analysis showed that IK positively regulated ofd1 expression required for cilium assembly. Downregulation of ofd1 expression upon depletion of IK led to ciliary defects that was rescued by restoration of ofd1 expression. Interestingly, IK affected ciliogenesis particularly in the proximal tubule but not in the distal tubule in the kidney. Conclusions This study demonstrates the role of IK in ciliogenesis in vivo for the first time. Loss of IK in zebrafish embryos displays various ciliopathy phenotypes with abnormal ciliary morphology in ciliary tissues. Our findings on the IK–OFD1 axis provide new insights into the biological function of IK in clinical ciliopathy studies in humans. Ciliopathy Ciliogenesis IK Oral-facial-digital syndrome OFD1 Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Full Text Supplementary Files AdditionalFile.pdf Cite Share Download PDF Status: Published Journal Publication published 28 Oct, 2023 Read the published version in Cell & Bioscience → Version 1 posted Reviewers agreed at journal 21 May, 2023 Reviewers invited by journal 18 May, 2023 Editor assigned by journal 10 May, 2023 First submitted to journal 04 May, 2023 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. 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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-2896500","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":201845052,"identity":"aac9e9dd-a1a1-440e-90ec-bef892ecf059","order_by":0,"name":"Hye In Ka","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA+UlEQVRIiWNgGAWjYBACCQYehgMfKmyATDaEKGMDAS0HZ5xJI1ELM2/bYRK0SLafPXiAh+28PT97W+pm3rY7dg3shx8wztyDW4s0T17CAQme24kze44du83b9iy5gSfNgHHDM9xa5BhyDA4YSNxOMLiR3gbUcjiZgSGHgfHBATxa+N8YHEgwOGeP0ML/Br8WaQmgLQcSDjBuuJEGcthhOwYJoC0b8GiRnPHG4GDDgWSQX9Juzjl3OIFN4pnBwRl4tEiczzH+/PefHSjEzG68KTtsz8+f/PBhDx4tKICJh4EhsQ3IIFYDMAZ/MDDYE616FIyCUTAKRgwAADNkWmZeckpqAAAAAElFTkSuQmCC","orcid":"https://orcid.org/0000-0002-1279-1220","institution":"Sookmyung Women's University","correspondingAuthor":true,"prefix":"","firstName":"Hye","middleName":"In","lastName":"Ka","suffix":""},{"id":201845053,"identity":"eb491603-774a-43ed-b814-67a12aed28f2","order_by":1,"name":"Mina Cho","email":"","orcid":"","institution":"Sookmyung Women's University","correspondingAuthor":false,"prefix":"","firstName":"Mina","middleName":"","lastName":"Cho","suffix":""},{"id":201845054,"identity":"8023c524-f35d-432b-8abb-4efdafc5ce1f","order_by":2,"name":"Seung-Hae Kwon","email":"","orcid":"","institution":"KBSI: Korea Basic Science Institute","correspondingAuthor":false,"prefix":"","firstName":"Seung-Hae","middleName":"","lastName":"Kwon","suffix":""},{"id":201845055,"identity":"53382623-165e-46b4-b3bb-adbd8c8e52e0","order_by":3,"name":"Se Hwan Mun","email":"","orcid":"","institution":"Sookmyung Women's University","correspondingAuthor":false,"prefix":"","firstName":"Se","middleName":"Hwan","lastName":"Mun","suffix":""},{"id":201845056,"identity":"5de2cc44-fb84-4fbf-a43a-47cb1d9062b5","order_by":4,"name":"Sora Han","email":"","orcid":"","institution":"Sookmyung Women's University","correspondingAuthor":false,"prefix":"","firstName":"Sora","middleName":"","lastName":"Han","suffix":""},{"id":201845057,"identity":"709fc112-8428-4885-8422-c7364b158192","order_by":5,"name":"Min Jung Kim","email":"","orcid":"","institution":"Sookmyung Women's University","correspondingAuthor":false,"prefix":"","firstName":"Min","middleName":"Jung","lastName":"Kim","suffix":""},{"id":201845058,"identity":"490e98d4-8622-453b-aa58-6fef08a8b358","order_by":6,"name":"Young Yang","email":"","orcid":"https://orcid.org/0000-0003-4239-0804","institution":"Sookmyung Women's University","correspondingAuthor":false,"prefix":"","firstName":"Young","middleName":"","lastName":"Yang","suffix":""}],"badges":[],"createdAt":"2023-05-05 05:29:35","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-2896500/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-2896500/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1186/s13578-023-01146-9","type":"published","date":"2023-10-28T15:01:33+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":37333478,"identity":"569222d7-8d91-4b47-a8ba-e865fb938a22","added_by":"auto","created_at":"2023-05-22 15:24:47","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":776326,"visible":true,"origin":"","legend":"\u003cp\u003ezebrafish ik mutants display ciliopathy-like phenotypes (A) Whole-mount in situ hybridization (WISH) analysis of zebrafish ik mRNA at different developmental stages (1-cell, 4-cell, 256-cell, Germ-ring, Bud, 14 somites, 1 dpf, 2 dpf, 3 dpf, and 4 dpf). Scale bar, 250 μm (B) Schematic representation of the coding region of zebrafish ik. The target region (exon 2) of the morpholino employed in this study was represented using a blue line (C) RT-PCR analysis of ik mRNA expression in control morphants (MO), ik MO, and ik MO/ik mRNA co-injected embryos at 2 dpf. gapdh served as a normalization control (D) Brightfield microscopic images of control MO, ik MO, and ik MO/ik mRNA co-injected embryos at 2 dpf. Whole body, otolith, and kidney cyst were captured. Pronephric cysts of ik MO are marked with red arrowhead (E) Brightfield microscopic images of the body curvature, otolith, and pronephric cysts pronephros in WT embryos and ik mutants (ik -/-) at 2 dpf. Pronephric cyst of ik mutants is marked with red arrowhead. Stacked bar graph displays the percentage of embryos with a ventrally curved body, abnormal otolith phenotype, and cyst formation (F) WISH analysis of cmlc2 for the location of whole heart in WT embryos and ik mutants at 2 dpf\u003c/p\u003e","description":"","filename":"Figures1.png","url":"https://assets-eu.researchsquare.com/files/rs-2896500/v1/5fd31af8c9d66fea304c8b17.png"},{"id":37333480,"identity":"752003b2-9336-40e1-908d-f640bdb649f5","added_by":"auto","created_at":"2023-05-22 15:24:47","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":1177343,"visible":true,"origin":"","legend":"\u003cp\u003eLoss of ik results in abnormal ciliary morphology (A) Confocal microscopic images of control MO, ik MO, and ik MO/ik mRNA co-injected Tg(brn3c:GFP) embryos at 3 dpf. Scale bar, 20 μm. Quantification of ciliary length and number in the inner ear of control MO, ik MO, and ik MO/ik mRNA co-injected embryos. **p \u0026lt; 0.01, ***p \u0026lt; 0.001 (B) Whole-mount immunofluorescence (left) of overall cilia in the pronephros of control MO, ik MO, and ik MO/ik mRNA co-injected embryos at 3 dpf with anti-acetylated-α-tubulin (green). Scale bar, 100 μm. Enlarged view (right) of pronephric cilia in the anterior and posterior pronephric ducts stained using anti-acetylated-α-tubulin (green) and nuclei stained with DAPI (blue) at 2 dpf control MO, ik MO, and ik MO/ ik mRNA co-injected embryos. Scale bar, 20 μm. Stacked bar graph displays the percentage of embryos based on ciliary morphology in the anterior pronephric duct (percentage of abnormal ciliary morphology of embryos: control MO, 0%; ik MO, 43.3%; ik MO + ik mRNA, 0%) (C) Whole-mount immunostaining of cilia in the inner ear (white boxes) using anti-acetylated-α-tubulin (green) of WT embryos and ik mutants at 2 dpf. Scale bar, 20 μm. Quantified graphs of cilia lengths and numbers in the inner ear between WT embryos and ik mutants at 2 dpf., ***p \u0026lt; 0.001, *p \u0026lt; 0.05. (D) Whole-mount immunofluorescence (left) of overall cilia in the pronephros in WT and in ik mutants at 2 dpf using anti-acetylated-α-tubulin (green). Scale bar, 100 μm. Enlarged view (right) of pronephric cilia in proximal and distal tubules stained with anti-acetylated-α-tubulin (green) and nuclei stained with DAPI (blue) at 2 dpf WT embryos and ik mutants. Scale bar, 20 μm. Stacked bar graph displays the percentage of embryos of cilia phenotype in the anterior pronephric duct of WT embryos and ik mutants at 2 dpf. (E) TEM results showing the ultrastructure of cilia in the pronephric duct of ik mutants. Cross-section showing the “9+2” configuration (black circles). Scale bar, 100 nm\u003c/p\u003e","description":"","filename":"Figures2.png","url":"https://assets-eu.researchsquare.com/files/rs-2896500/v1/cd10219196594da1c5fff8c4.png"},{"id":37333479,"identity":"c44f55d1-6cd8-4a91-af68-582a1b9b3f2b","added_by":"auto","created_at":"2023-05-22 15:24:47","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":525000,"visible":true,"origin":"","legend":"\u003cp\u003eik mutants show impaired kidney development with abnormal cilia morphology (A) WISH analysis of pronephric duct markers slc4a4, slc13a1, and slc12a3 in WT embryos and ik mutants at 2 dpf. Scale bar, 250 μm (B) RT-PCR analysis of slc4a4, slc13a1, and slc12a3 expression in WT embryos and ik mutants at 2 dpf. gapdh served as a normalization control. Relative bands intensities of slc4a4, slc13a1, and slc12a3 normalized to gapdh intensity was graphically represented (in triplicates) using Image J software. **p \u0026lt; 0.01, ***p \u0026lt; 0.001 (C) Linear filter model showing correlation of overall gene expression based on RNA-seq data between WT and ik mutants at 3 dpf. The point of foxj1a plot is indicated. (D) RT-PCR analysis of foxj1a expression in WT embryos and ik mutants at 1.5 and 2.5 dpf. gapdh served as a normalization control. Relative band intensity of foxj1a normalized with respect to gapdh intensity is graphically represented (in triplicates) (E) WISH analysis of foxj1a in WT and ik mutants at 1.5, 2, and 2.5 dpf. Scale bar, 250 μm (F) WISH analysis of foxj1a in control MO, ik MO, and ik MO/ik mRNA co-injected embryos at 2.5 dpf. Scale bar, 250 μm\u003c/p\u003e","description":"","filename":"Figures3.png","url":"https://assets-eu.researchsquare.com/files/rs-2896500/v1/2d6a63ee935d4eba690ddeb9.png"},{"id":37332568,"identity":"645fad7f-6993-4710-9421-1c356f6929e5","added_by":"auto","created_at":"2023-05-22 15:16:47","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":555073,"visible":true,"origin":"","legend":"\u003cp\u003eofd1, a necessary gene for cilia assembly, is downregulated by the loss of ik (A) Heat map of seven differentially expressed cilium assembly genes at least 1.5 \u0026gt; log2 fold changes in ik mutants relative to those of WT embryos. Upregulated DEGs relative to the mean are indicated by red color. Downregulated DEGs are shown by blue color (scale bar, log 2 of mRNA ratio) (B) RT-PCR analysis of ofd1 mRNA expression in WT embryos and ik mutants. gapdh served as a normalization control. Relative band intensity of ofd1 normalized with respect to gapdh intensity is graphically represented (in triplicate) using Image J software. **p \u0026lt; 0.01 (C) WISH for ofd1 in WT embryos and ik mutants at 1 dpf. Scale bar, 100 μm. Enlarged view of the pronephros in WT and ik mutants at 1 dpf. Scale bar, 150 μm (D) RT-PCR analysis of ofd1 mRNA expression in control MO, ik MO, and ik MO/ik mRNA co-injected embryos at 1.5 dpf. gapdh served as a normalization control. Relative band intensity of ofd1 normalized with respect to gapdh intensity is graphically represented (in three individual experiments) using Image J software. **p \u0026lt; 0.01, ***p \u0026lt; 0.001 (E) WISH for ofd1 in control MO, ik MO, and ik MO/ik mRNA co-injected embryos at 1 dpf. Enlarged view of the pronephros in control MO, ik MO, and ik MO/ik mRNA co-injected embryos at 1 dpf. Scale bar, 100 μm\u003c/p\u003e","description":"","filename":"Figures4.png","url":"https://assets-eu.researchsquare.com/files/rs-2896500/v1/ef7469a727e1225b8764c804.png"},{"id":37332569,"identity":"56a822b9-fdf3-446b-9c72-bbdbb003453c","added_by":"auto","created_at":"2023-05-22 15:16:47","extension":"png","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":780458,"visible":true,"origin":"","legend":"\u003cp\u003eThe ciliopathy phenotypes of ik mutants are rescued by ofd1 co-injection (A) The lateral morphological view of control MO, ik MO, and ik MO/ofd1 mRNA co-injected embryos (body curvature and otolith imaged at 2 dpf and pronephric cyst imaged at 3 dpf). Pronephric cyst in ik MO is indicated by red arrowhead. Stacked bar graph displays the phenotypic percentage of embryos. (B) WISH for ofd1 in control MO, ik MO, and ik MO/ofd1 mRNA co-injected embryos at 1 dpf. Scale bar, 100 μm. Enlarged view of the pronephros in control MO, ik MO, and ik MO/ik mRNA co-injected embryos at 1 dpf. Scale bar, 150 μm. (C) WISH for foxj1a in control MO, ik MO, and ik MO/ofd1 mRNA co-injected embryos at 2.5 dpf. Scale bar, 100 μm (D) RT-PCR analysis of ofd1 mRNA expression in control MO, ik MO, and ik MO/ofd1 mRNA co-injected embryos at 1.5 dpf. gapdh served as a normalization control. Relative band intensity of ofd1 normalized with respect to gapdh intensity is graphically represented using Image J software (in three individual experiments). *p \u0026lt; 0.05, ***p \u0026lt; 0.001\u003c/p\u003e","description":"","filename":"Figures5.png","url":"https://assets-eu.researchsquare.com/files/rs-2896500/v1/08d17f309bb5bbc83020dcf5.png"},{"id":37332571,"identity":"108d8c48-21fe-4f53-b1d9-0b45831c3e77","added_by":"auto","created_at":"2023-05-22 15:16:47","extension":"png","order_by":6,"title":"Figure 6","display":"","copyAsset":false,"role":"figure","size":398857,"visible":true,"origin":"","legend":"\u003cp\u003eofd1 co-injection can rescue ciliary dysmorphology of ik morphants (A) Confocal microscopic images of control MO, ik MO, and ik MO/ofd1 mRNA co-injected Tg(brn3c:GFP) embryos at 2 dpf. Scale bar, 20 μm. Bar graphs show quantification of ciliary length and number in the inner ears of control MO, ik MO, and ik MO/ofd1 mRNA co-injected embryos at 2 dpf. **p \u0026lt; 0.01, ***p \u0026lt; 0.001 (B) Whole-mount immunostaining of pronephric cilia using anti-acetylated-α-tubulin (red) at 2 dpf control MO, ik MO, and ik MO/ ofd1 mRNA co-injected embryos. Scale bar, 20 μm. Stacked bar graph displays the percentage of ciliary morphology of embryos in the anterior pronephric duct (percentage of abnormal ciliary morphology of embryos: control MO, 5.12% (37/39); ik MO, 86.6 % (4/30); ik MO+ofd1 mRNA, 16.6% (15/18)\u003c/p\u003e","description":"","filename":"Figures6.png","url":"https://assets-eu.researchsquare.com/files/rs-2896500/v1/47fa4b4dd1a7b72b5f243b95.png"},{"id":45453745,"identity":"c9de36b0-25c6-4eb5-b03e-8e623a0f9e69","added_by":"auto","created_at":"2023-10-30 15:05:58","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":842835,"visible":true,"origin":"","legend":"","description":"","filename":"Manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-2896500/v1_covered_d5c439e2-278e-449d-a3d9-9b404df8fc46.pdf"},{"id":37332573,"identity":"6294636a-d442-4187-a3ba-7a9f207e4740","added_by":"auto","created_at":"2023-05-22 15:16:47","extension":"pdf","order_by":6,"title":"","display":"","copyAsset":false,"role":"supplement","size":2596313,"visible":true,"origin":"","legend":"","description":"","filename":"AdditionalFile.pdf","url":"https://assets-eu.researchsquare.com/files/rs-2896500/v1/7a3eca3a26fd39c319377265.pdf"}],"financialInterests":"","formattedTitle":"IK is essentially involved in ciliogenesis as an upstream regulator of oral-facial-digital syndrome ciliopathy gene,ofd1","fulltext":[],"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":true,"isPdf":true,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"cell-and-bioscience","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"cbio","sideBox":"Learn more about [Cell \u0026 Bioscience](http://cellandbioscience.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/cbio/default.aspx","title":"Cell \u0026 Bioscience","twitterHandle":"@OACellBiology","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Ciliopathy, Ciliogenesis, IK, Oral-facial-digital syndrome, OFD1","lastPublishedDoi":"10.21203/rs.3.rs-2896500/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-2896500/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"Background\nThe cilia are microtubule-based organelles that protrude from the cell surface. Abnormalities in cilia result in various ciliopathies, including polycystic kidney disease (PKD), Bardet-Biedl syndrome (BBS), and oral-facial-digital syndrome type I (OFD1), which show genetic defects associated with cilia formation. Although an increasing number of human diseases is attributed to ciliary defects, the functions or regulatory mechanisms of several ciliopathy genes remain unclear. Because cilia are deep in vivo, studying ciliogenesis is challenging. Here, we demonstrate that IK is essential for ciliogenesis in vivo.\nResults\nIn the absence of IK, zebrafish embryos showed various ciliopathy phenotypes, such as body curvature, abnormal otoliths, and cyst formation in the kidney. RNA sequencing analysis showed that IK positively regulated ofd1 expression required for cilium assembly. Downregulation of ofd1 expression upon depletion of IK led to ciliary defects that was rescued by restoration of ofd1 expression. Interestingly, IK affected ciliogenesis particularly in the proximal tubule but not in the distal tubule in the kidney.\nConclusions\nThis study demonstrates the role of IK in ciliogenesis in vivo for the first time. Loss of IK in zebrafish embryos displays various ciliopathy phenotypes with abnormal ciliary morphology in ciliary tissues. Our findings on the IK–OFD1 axis provide new insights into the biological function of IK in clinical ciliopathy studies in humans.","manuscriptTitle":"IK is essentially involved in ciliogenesis as an upstream regulator of oral-facial-digital syndrome ciliopathy gene,ofd1","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2023-05-22 15:16:42","doi":"10.21203/rs.3.rs-2896500/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"reviewerAgreed","content":"","date":"2023-05-21T08:19:11+00:00","index":0,"fulltext":""},{"type":"reviewersInvited","content":"","date":"2023-05-19T00:10:39+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2023-05-10T13:12:23+00:00","index":"","fulltext":""},{"type":"submitted","content":"Cell \u0026 Bioscience","date":"2023-05-05T01:29:21+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"cell-and-bioscience","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"cbio","sideBox":"Learn more about [Cell \u0026 Bioscience](http://cellandbioscience.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/cbio/default.aspx","title":"Cell \u0026 Bioscience","twitterHandle":"@OACellBiology","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"7e036049-0a66-43d3-b296-4b2acc7463b6","owner":[],"postedDate":"May 22nd, 2023","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2023-10-30T15:03:17+00:00","versionOfRecord":{"articleIdentity":"rs-2896500","link":"https://doi.org/10.1186/s13578-023-01146-9","journal":{"identity":"cell-and-bioscience","isVorOnly":false,"title":"Cell \u0026 Bioscience"},"publishedOn":"2023-10-28 15:01:33","publishedOnDateReadable":"October 28th, 2023"},"versionCreatedAt":"2023-05-22 15:16:42","video":"","vorDoi":"10.1186/s13578-023-01146-9","vorDoiUrl":"https://doi.org/10.1186/s13578-023-01146-9","workflowStages":[]},"version":"v1","identity":"rs-2896500","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-2896500","identity":"rs-2896500","version":["v1"]},"buildId":"_2-kVJe1T_tPrBINL-cwx","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}