Evaluating and comparing the signalling and functional landscape of iPSC- CMs derived from patients with dilated cardiomyopathy

Evaluating and comparing the signalling and functional landscape of iPSC- CMs derived from patients with dilated cardiomyopathy | 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 Evaluating and comparing the signalling and functional landscape of iPSC- CMs derived from patients with dilated cardiomyopathy Giada Castagnola, Diego Loggia, Kyla Bourque, Karima Alim, Ida Derish, and 11 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8633189/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 11 You are reading this latest preprint version Abstract Non-ischemic or dilated cardiomyopathy (DCM) is characterized by abnormal enlargement of the left ventricle, compromising the ability of the heart to pump blood to the body. All patients with DCM are offered the same treatment regimen regardless of individual differences, with highly variable results on disease progression. Some patients fully recover cardiac function, while others continue to deteriorate, requiring heart replacement therapy or palliation. Incomplete molecular knowledge of dilated cardiomyopathy pathophysiology poses challenges for discovery of new therapeutic agents. To address this, we use induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) to assess individual molecular signalling and functional signatures in patients with DCM. Using blood samples from two healthy controls and two patients with DCM, we generated and validated iPSC lines, then differentiated them into cardiomyocytes. Cellular signalling was assessed in each iPSC-CM line after treatment with several disease-relevant G protein-coupled receptor (GPCR)-targeting ligands, measured using nuclear and cytosolic PKA and ERK biosensors at single cell resolution. Differences in functional properties such as calcium handling, contractility, and electrophysiology revealed additional features altered in patients with DCM. We have now established a pipeline to uncover patient-specific molecular mechanisms and disease phenotypes as a pathway to the development of personalized treatment for DCM. One Sentence Summary : Building a pipeline for bench-to-bedside study of DCM Biological sciences/Biological techniques Health sciences/Cardiology Biological sciences/Stem cells Full Text Additional Declarations No competing interests reported. Supplementary Files CastagnolaLoggiaFinalSupplementaryFigures.pdf SupplementaryFigurelegends.pdf Cite Share Download PDF Status: Under Review Version 1 posted Editorial decision: Revision requested 25 Feb, 2026 Reviews received at journal 15 Feb, 2026 Reviews received at journal 05 Feb, 2026 Reviews received at journal 05 Feb, 2026 Reviewers agreed at journal 30 Jan, 2026 Reviewers agreed at journal 27 Jan, 2026 Reviewers agreed at journal 23 Jan, 2026 Reviewers invited by journal 23 Jan, 2026 Editor assigned by journal 22 Jan, 2026 Submission checks completed at journal 22 Jan, 2026 First submitted to journal 18 Jan, 2026 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-8633189","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":582088426,"identity":"eb504007-bcf2-425d-8398-f4b3c0d27df9","order_by":0,"name":"Giada Castagnola","email":"","orcid":"","institution":"McGill University","correspondingAuthor":false,"prefix":"","firstName":"Giada","middleName":"","lastName":"Castagnola","suffix":""},{"id":582088427,"identity":"03dd2023-25cb-42f7-b864-6f8e29c0c855","order_by":1,"name":"Diego Loggia","email":"","orcid":"","institution":"McGill 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