A silkworm model reveals coordinated cellular communities and conserved Hippo regulation in silk production | 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 A silkworm model reveals coordinated cellular communities and conserved Hippo regulation in silk production Hanfu Xu, Yan Ma, Zhiyong Zhang, Wenhui Zeng, 舟 方, Jie Hu, Yiyun Tang, and 13 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7747598/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 Silk production, a spectacular evolutionary innovation shared by approximately 143,000 arthropod species, is underpinned by genetic and cellular programs that remain incompletely resolved. Although a cellular atlas exists for the silkworm (Bombyx) silk gland (SG)—the premier model for this trait—the coordinated cellular dynamics and transcriptional logic that underlie its remarkable efficiency are unsolved. Here, we bridge this gap by an integrative meta-analysis that leverages single-cell deconvolution and high-dimensional weighted gene coexpression network analysis (hdWGCNA). Applied to existing atlases, public data, and de novo transcriptomes, this computational strategy enabled the identification of key cell subpopulations and the reconstruction of a high-resolution, global coexpression network orchestrating silk production. This network nominated the Hippo signaling pathway as a top regulatory hub. Functionally, conditional overexpression and knockout of its core effector, Yorkie (Yki), demonstrated that Yki is causal for SG development and silk protein synthesis. Further deconvolution of Yki-mutant transcriptomes confirmed the substantial impact of Hippo–Yki signaling on the cellular hierarchical framework of the SG. Our work not only deciphers a key regulatory axis controlling a classic biological trait but also provides an integrative computationally driven experimental framework, establishing a paradigm for obtaining mechanistic insights from complex omics landscapes. Biological sciences/Molecular biology/Transcriptomics Biological sciences/Genetics/Gene regulation Biological sciences/Computational biology and bioinformatics/Gene regulatory networks Biological sciences/Genetics/Gene expression Biological sciences/Developmental biology/Experimental organisms/Transgenic organisms Full Text Additional Declarations There is NO Competing Interest. Supplementary Files 3Supplementaryinformation2025.9.30.pdf Supplementary information AdditionalSupplementaryFiles2025.9.30.zip Supplementary Dataset 21 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-7747598","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":522746798,"identity":"cbb162d1-23d4-442e-8238-3f0ed2e268cd","order_by":0,"name":"Hanfu 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