Single-Cell Transcriptomics Uncover IBSP as a Mediator of Tumor-Associated Microglia and Macrophages-Driven Glioblastoma Progression

Single-Cell Transcriptomics Uncover IBSP as a Mediator of Tumor-Associated Microglia and Macrophages-Driven Glioblastoma Progression | 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 Transcriptomics Uncover IBSP as a Mediator of Tumor-Associated Microglia and Macrophages-Driven Glioblastoma Progression Atul Anand, Rikke Frydendahl Sick Olsen, Dylan Harwood, Mark Burton, and 22 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6573801/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Tumor-associated microglia and macrophages (TAMs) represent the second largest cellular population in glioblastoma and play a pivotal role in tumor progression. However, the transcriptional landscape underlying CD11b + TAM heterogeneity remains poorly characterized. Here, we employ single-cell RNA sequencing to dissect and compare the heterogeneity of CD11b + TAMs in glioblastoma versus non-tumor control tissue, identifying a distinct subpopulation expressing integrin-binding sialoprotein (IBSP). Spatial analyses using GeoMx and immunofluorescence staining reveal that IBSP expression is predominantly localized to TAMs residing in perivascular niches and pseudo-palisades. Functionally, we show that glioblastoma-derived TAMs secrete IBSP, which enhances self-renewal in patient-derived glioblastoma models. Transcriptomic profiling of IBSP-stimulated glioblastoma cells demonstrates upregulation of Inhibitor of DNA Binding ( ID ) genes, suggesting that IBSP promotes tumor aggressiveness by activating pro-tumorigenic pathways. These findings identify IBSP-positive TAMs as a novel subpopulation with critical roles in shaping the glioblastoma microenvironment and position IBSP as a promising therapeutic target for disrupting tumor-supportive niches in glioblastoma. Biological sciences/Immunology/Tumour immunology Biological sciences/Immunology/Neuroimmunology Full Text Additional Declarations Yes there is potential Competing Interest. JDL reports being named as a co-inventor on pending and issued patents held by the Cleveland Clinic relating to cancer therapies, but these are not directly relevant to this work. Supplementary Files ExtendedFigures18.pdf FigureLegendExtendedDataFigure.pdf Cite Share Download PDF Status: Posted 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-6573801","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":470787882,"identity":"3d6c0fa6-21dc-40e0-8430-97b5699bfed3","order_by":0,"name":"Atul 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