NADH-DLEM-seq: A High-Fidelity Multimodal Platform Revealing Fiber-Type-Specific Metabolic and Transcriptional Remodeling in Sarcopenia

NADH-DLEM-seq: A High-Fidelity Multimodal Platform Revealing Fiber-Type-Specific Metabolic and Transcriptional Remodeling in Sarcopenia | 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 NADH-DLEM-seq: A High-Fidelity Multimodal Platform Revealing Fiber-Type-Specific Metabolic and Transcriptional Remodeling in Sarcopenia Bei Li, Fuyuan Chen, Shi Chen, Meina Chen, Mengting Ming, Tao Xiong, and 4 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-9027627/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 Unraveling the spatial heterogeneity of tissue microenvironments is essential for understanding complex pathologies like sarcopenia. However, existing spatial omics technologies often compromise between single-cell resolution, macromolecular integrity, and metabolic context. Here, we present "Donut" Laser Ejection Microdissection (DLEM), a high-throughput, non-contact spatial sampling platform. By integrating Spatial Light Modulator (SLM)-based vortex beam shaping with a metal-assisted ejection mechanism, DLEM achieves subcellular precision (5µm) and "cold-cutting" isolation, fundamentally eliminating thermal damage. This ensures superior RNA quality, maintaining > 82.5% genome alignment rates even at the single-cell level. We developed a multimodal NADH-DLEM-seq workflow to link in situ metabolic phenotypes with transcriptomic profiles. Applying this to a murine model of chronic kidney disease (CKD)-induced sarcopenia, we dissected the distinct molecular trajectories of oxidative (Type I) and glycolytic (Type IIB) myofibers. We reveal a dichotomous response to stress: Type I fibers undergo profibrotic remodeling via collagen signaling activation, whereas Type IIB fibers exhibit pronounced catabolic atrophy and mitochondrial disassembly. These findings, obscured in bulk analyses, underscore DLEM as a powerful tool for deciphering the metabolic-transcriptional coupling in aging and disease, offering precise targets for therapeutic intervention in sarcopenia. Biological sciences/Biological techniques/Lab-on-a-chip Biological sciences/Biological techniques/Metabolomics Laser Ejection Microdissection Beam Shaping Photomechanical ejection Full-length single-cell sequencing Skeletal muscle heterogeneity Full Text Additional Declarations There is NO Competing Interest. Supplementary Files SupplementaryMaterial.docx NADH-DLEM-seq: A High-Fidelity Multimodal Platform Revealing Fiber-Type-Specific Metabolic and Transcriptional Remodeling in Sarcopenia 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. 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-9027627","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":611789906,"identity":"66127bac-80dc-4d61-8bf9-f96859d919be","order_by":0,"name":"Bei 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