Metabolic Reallocation in the Tumor Microenvironment of Colorectal Cancer at Single-cell Resolution

Metabolic Reallocation in the Tumor Microenvironment of Colorectal Cancer at Single-cell Resolution | 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 Metabolic Reallocation in the Tumor Microenvironment of Colorectal Cancer at Single-cell Resolution Ziwei Dai, Dan Huang This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-5978633/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted You are reading this latest preprint version Abstract Metabolic reprogramming of diverse cell types within the tumor microenvironment (TME) is crucial for tumor progression. While previous single-cell studies have identified a set of up- or down-regulated pathways, they often overlook the broader question of how metabolic activity is dynamically allocated among competing processes. Here we present a computational framework integrating multiple single-cell transcriptomic datasets for human colorectal cancer (CRC) to quantify metabolic resource allocation strategies in the TME. Our analysis revealed cell-type-specific metabolic reallocation occurring at both global and local levels and a diverse mode of regulation of metabolic reallocation by novel signaling modules, metabolic reallocation regulators (MRRs), that occur specifically in cancer cells, suggesting a complex network of signaling-metabolism crosstalk during cancer progression. Activities of these MRRs are significantly associated with biological and clinical features of the tumors, highlighting the critical role of metabolic reallocation in cancer progression. By characterizing the metabolic plasticity of the TME and its regulatory drivers, this study advances our understanding of CRC metabolism and offers insights into precision medicine strategies targeting metabolic dependencies. Biological sciences/Cancer/Cancer metabolism Biological sciences/Systems biology/Biochemical networks Full Text Additional Declarations There is NO Competing Interest. Supplementary Files CRCscRNAseqSupplementaryTable1ZD202502.xlsx Supplementary Table 1 CRCscRNAseqSIZD202502.docx Supplementary Information Cite Share Download PDF Status: Under Review 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. 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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-5978633","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":419050202,"identity":"559bc456-4796-4c03-9806-5d7b13f97a26","order_by":0,"name":"Ziwei Dai","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA3UlEQVRIiWNgGAWjYDCCA4wNDAwVEDYzEIO4xGg5A2SwEa8FpKyNFC18xw83f+adV5c4f37zwc8FDDayGw4wP3uAT4vkmcQGY95thxM3HGNLlp7BkGa84QCbuQE+LQYHEhuSc7cdSNzAxmPGzMMA1HuAh00Cr5bzDxsO584BOqyN/xtQy38itNxIbGzObWBObDjGwwbUcoCwFskbD5uZ/xw7bLzhWJqxNI9BsvHMw2xmeLXwnU9//HFGTZ3s/ObDDz/zVNjJ9h1vfoZXC7o7GSCxMwpGwSgYBaOAMgAA389MHKOC9yQAAAAASUVORK5CYII=","orcid":"https://orcid.org/0000-0002-0858-638X","institution":"Southern University of Science and Technology","correspondingAuthor":true,"prefix":"","firstName":"Ziwei","middleName":"","lastName":"Dai","suffix":""},{"id":419050203,"identity":"f0ca869d-bf7d-41f3-b3ed-eee277475db2","order_by":1,"name":"Dan Huang","email":"","orcid":"https://orcid.org/0000-0003-3022-5772","institution":"Southern University of Science and Technology","correspondingAuthor":false,"prefix":"","firstName":"Dan","middleName":"","lastName":"Huang","suffix":""}],"badges":[],"createdAt":"2025-02-07 07:15:29","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-5978633/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-5978633/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":80421134,"identity":"7f0375f7-cf1e-4715-84d4-2c2c6fc08c63","added_by":"auto","created_at":"2025-04-11 18:56:08","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":420475,"visible":true,"origin":"","legend":"","description":"","filename":"CRCscRNAseqmanuscriptZD202502HD.pdf","url":"https://assets-eu.researchsquare.com/files/rs-5978633/v1_covered_fccd7022-213f-430a-b074-1d9256d205ee.pdf"},{"id":80420583,"identity":"a1acb39f-26e9-456a-92d6-cc7dec9a93bd","added_by":"auto","created_at":"2025-04-11 18:48:04","extension":"xlsx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":177481,"visible":true,"origin":"","legend":"Supplementary Table 1","description":"","filename":"CRCscRNAseqSupplementaryTable1ZD202502.xlsx","url":"https://assets-eu.researchsquare.com/files/rs-5978633/v1/ea90f1ffd5fe60afd07172e2.xlsx"},{"id":80420224,"identity":"f58d4d10-acc4-4fe4-872b-4482c3104fcb","added_by":"auto","created_at":"2025-04-11 18:40:04","extension":"docx","order_by":2,"title":"","display":"","copyAsset":false,"role":"supplement","size":27996788,"visible":true,"origin":"","legend":"Supplementary Information","description":"","filename":"CRCscRNAseqSIZD202502.docx","url":"https://assets-eu.researchsquare.com/files/rs-5978633/v1/0e9583bd97eeae84662703ff.docx"}],"financialInterests":"There is \u003cb\u003eNO\u003c/b\u003e Competing Interest.","formattedTitle":"Metabolic Reallocation in the Tumor Microenvironment of Colorectal Cancer at Single-cell Resolution","fulltext":[],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":false,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"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-5978633/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-5978633/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eMetabolic reprogramming of diverse cell types within the tumor microenvironment (TME) is crucial for tumor progression. 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