Developmental restriction of the jaw skeletal muscle cardiogenic potential

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This preprint studied whether stem/progenitor cells from jaw (masticatory) skeletal muscle can be induced into cardiomyocytes or cardiac cells, testing satellite cells and mesenchymal progenitor cells using reproduced, optimized, and diversified cardiogenic differentiation protocols. The key finding was that masticatory muscle stem cells were consistently unable to differentiate into cardiac cells in any tested cardiogenic environment, despite a developmental link between jaw muscles and the right ventricular myocardium. A major caveat stated in the abstract is that pharmacological “erasing” of repressive epigenetic marks did not activate cardiogenic potential, implying strong lineage barriers and limiting prospects for reversal by simple environmental exposure. The paper does not explicitly discuss endometriosis or adenomyosis; it was included in the corpus via a keyword match in the upstream search index.

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Abstract

Abstract Cardiovascular diseases are a leading cause of mortality worldwide and heart failure remains an end-stage disease with no other treatment than transplantation. A promising field to tackle heart failure is cardiomyocyte implantation. Whereas cardiomyocyte generation from pluripotent cells has shown promising results, direct derivation of cardiomyocytes from somatic stem cells is still challenging. Skeletal muscle progenitors have been extensively studied as a source of cardiac cells, due to their cellular and functional similarities. During development, the right ventricular myocardium and jaw skeletal muscles derive from a common pool of myogenic mesodermal progenitors. Previous studies have reported the derivation of cardiomyocyte-like cells specifically from adult jaw muscle stem cell populations, but not from other skeletal muscles, suggesting that developmental origin endows cardiogenic potential. Here we evaluated the cardiogenic potential of satellite cells and mesenchymal progenitor cells from the masticatory muscle by reproducing, optimizing and diversifying previously described protocols. We consistently found that stem cells from masticatory muscles are unable to differentiate into cardiac cells under any tested cardiogenic environment. Furthermore, pharmacological erasing of repressive epigenetic marks did not activate cardiogenic potential, suggesting that barriers restraining lineage plasticity are profound and unlikely to be reversed by simple exposure to cardiogenic environments.
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Developmental restriction of the jaw skeletal muscle cardiogenic potential | 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 Developmental restriction of the jaw skeletal muscle cardiogenic potential Miguel Torres, Covadonga Diaz-Diaz, Oscar Ocaña, Joan Isern, Pura Munoz-Canoves This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7928886/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 Cardiovascular diseases are a leading cause of mortality worldwide and heart failure remains an end-stage disease with no other treatment than transplantation. A promising field to tackle heart failure is cardiomyocyte implantation. Whereas cardiomyocyte generation from pluripotent cells has shown promising results, direct derivation of cardiomyocytes from somatic stem cells is still challenging. Skeletal muscle progenitors have been extensively studied as a source of cardiac cells, due to their cellular and functional similarities. During development, the right ventricular myocardium and jaw skeletal muscles derive from a common pool of myogenic mesodermal progenitors. Previous studies have reported the derivation of cardiomyocyte-like cells specifically from adult jaw muscle stem cell populations, but not from other skeletal muscles, suggesting that developmental origin endows cardiogenic potential. Here we evaluated the cardiogenic potential of satellite cells and mesenchymal progenitor cells from the masticatory muscle by reproducing, optimizing and diversifying previously described protocols. We consistently found that stem cells from masticatory muscles are unable to differentiate into cardiac cells under any tested cardiogenic environment. Furthermore, pharmacological erasing of repressive epigenetic marks did not activate cardiogenic potential, suggesting that barriers restraining lineage plasticity are profound and unlikely to be reversed by simple exposure to cardiogenic environments. Biological sciences/Stem cells/Stem-cell differentiation Biological sciences/Stem cells/Muscle stem cells Biological sciences/Developmental biology/Transdifferentiation Biological sciences/Developmental biology/Epigenetic memory Full Text Additional Declarations There is NO Competing Interest. 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. 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