Sarcomere Disassembly and Transfection Efficiency in Proliferating Human iPSC-Derived Cardiomyocytes
Contractility of the adult heart relates to the architectural degree of sarcomeres in individual cardiomyocytes (CMs) and appears to be inversely correlated with the ability to regenerate. In this study we utilized multiple imaging techniques to follow the sequence of sarcomere disassembly during mi...
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MDPI AG
2022-01-01
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author | Qianliang Yuan Renee G. C. Maas Ellen C. J. Brouwer Jiayi Pei Christian Snijders Blok Marko A. Popovic Nanne J. Paauw Niels Bovenschen Jesper Hjortnaes Magdalena Harakalova Pieter A. Doevendans Joost P. G. Sluijter Jolanda van der Velden Jan W. Buikema |
author_facet | Qianliang Yuan Renee G. C. Maas Ellen C. J. Brouwer Jiayi Pei Christian Snijders Blok Marko A. Popovic Nanne J. Paauw Niels Bovenschen Jesper Hjortnaes Magdalena Harakalova Pieter A. Doevendans Joost P. G. Sluijter Jolanda van der Velden Jan W. Buikema |
author_sort | Qianliang Yuan |
collection | DOAJ |
description | Contractility of the adult heart relates to the architectural degree of sarcomeres in individual cardiomyocytes (CMs) and appears to be inversely correlated with the ability to regenerate. In this study we utilized multiple imaging techniques to follow the sequence of sarcomere disassembly during mitosis resulting in cellular or nuclear division in a source of proliferating human pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs). We observed that both mono- and binuclear hiPSC-CMs give rise to mononuclear daughter cells or binuclear progeny. Within this source of highly proliferative hiPSC-CMs, treated with the CHIR99021 small molecule, we found that Wnt and Hippo signaling was more present when compared to metabolic matured non-proliferative hiPSC-CMs and adult human heart tissue. Furthermore, we found that CHIR99021 increased the efficiency of non-viral vector incorporation in high-proliferative hiPSC-CMs, in which fluorescent transgene expression became present after the chromosomal segregation (M phase). This study provides a tool for gene manipulation studies in hiPSC-CMs and engineered cardiac tissue. Moreover, our data illustrate that there is a complex biology behind the cellular and nuclear division of mono- and binuclear CMs, with a shared-phenomenon of sarcomere disassembly during mitosis. |
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last_indexed | 2024-03-09T21:42:13Z |
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spelling | doaj.art-77a142c175a14adfbbc23f6f57c66fb62023-11-23T20:28:17ZengMDPI AGJournal of Cardiovascular Development and Disease2308-34252022-01-01924310.3390/jcdd9020043Sarcomere Disassembly and Transfection Efficiency in Proliferating Human iPSC-Derived CardiomyocytesQianliang Yuan0Renee G. C. Maas1Ellen C. J. Brouwer2Jiayi Pei3Christian Snijders Blok4Marko A. Popovic5Nanne J. Paauw6Niels Bovenschen7Jesper Hjortnaes8Magdalena Harakalova9Pieter A. Doevendans10Joost P. G. Sluijter11Jolanda van der Velden12Jan W. Buikema13Amsterdam Cardiovascular Sciences, Department of Physiology, Amsterdam University Medical Centers, De Boelelaan 1108, 1081 HZ Amsterdam, The NetherlandsUtrecht Regenerative Medicine Center, Circulatory Health Laboratory, University Utrecht, 3584 CS Utrecht, The NetherlandsAmsterdam Cardiovascular Sciences, Department of Physiology, Amsterdam University Medical Centers, De Boelelaan 1108, 1081 HZ Amsterdam, The NetherlandsUtrecht Regenerative Medicine Center, Circulatory Health Laboratory, University Utrecht, 3584 CS Utrecht, The NetherlandsUtrecht Regenerative Medicine Center, Circulatory Health Laboratory, University Utrecht, 3584 CS Utrecht, The NetherlandsDepartment of Molecular Cell Biology and Immunology (MCBI), Amsterdam University Medical Centers, De Boelelaan 1108, 1081 HZ Amsterdam, The NetherlandsDepartment of Molecular Cell Biology and Immunology (MCBI), Amsterdam University Medical Centers, De Boelelaan 1108, 1081 HZ Amsterdam, The NetherlandsBachelor Research Hub, Educational Center, University Medical Centre Utrecht, 3584 CX Utrecht, The NetherlandsDepartment of Cardiothoracic Surgery, Heart & Lung Center, Leiden University Medical Center, Leiden University, Albinusdreef 2, 2333 ZA Leiden, The NetherlandsUtrecht Regenerative Medicine Center, Circulatory Health Laboratory, University Utrecht, 3584 CS Utrecht, The NetherlandsUtrecht Regenerative Medicine Center, Circulatory Health Laboratory, University Utrecht, 3584 CS Utrecht, The NetherlandsUtrecht Regenerative Medicine Center, Circulatory Health Laboratory, University Utrecht, 3584 CS Utrecht, The NetherlandsAmsterdam Cardiovascular Sciences, Department of Physiology, Amsterdam University Medical Centers, De Boelelaan 1108, 1081 HZ Amsterdam, The NetherlandsAmsterdam Cardiovascular Sciences, Department of Physiology, Amsterdam University Medical Centers, De Boelelaan 1108, 1081 HZ Amsterdam, The NetherlandsContractility of the adult heart relates to the architectural degree of sarcomeres in individual cardiomyocytes (CMs) and appears to be inversely correlated with the ability to regenerate. In this study we utilized multiple imaging techniques to follow the sequence of sarcomere disassembly during mitosis resulting in cellular or nuclear division in a source of proliferating human pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs). We observed that both mono- and binuclear hiPSC-CMs give rise to mononuclear daughter cells or binuclear progeny. Within this source of highly proliferative hiPSC-CMs, treated with the CHIR99021 small molecule, we found that Wnt and Hippo signaling was more present when compared to metabolic matured non-proliferative hiPSC-CMs and adult human heart tissue. Furthermore, we found that CHIR99021 increased the efficiency of non-viral vector incorporation in high-proliferative hiPSC-CMs, in which fluorescent transgene expression became present after the chromosomal segregation (M phase). This study provides a tool for gene manipulation studies in hiPSC-CMs and engineered cardiac tissue. Moreover, our data illustrate that there is a complex biology behind the cellular and nuclear division of mono- and binuclear CMs, with a shared-phenomenon of sarcomere disassembly during mitosis.https://www.mdpi.com/2308-3425/9/2/43iPSC-derived cardiomyocyteshuman iPSCsarcomere developmentsarcomere disassemblytransfection efficiencynon-viral vector incorporation |
spellingShingle | Qianliang Yuan Renee G. C. Maas Ellen C. J. Brouwer Jiayi Pei Christian Snijders Blok Marko A. Popovic Nanne J. Paauw Niels Bovenschen Jesper Hjortnaes Magdalena Harakalova Pieter A. Doevendans Joost P. G. Sluijter Jolanda van der Velden Jan W. Buikema Sarcomere Disassembly and Transfection Efficiency in Proliferating Human iPSC-Derived Cardiomyocytes Journal of Cardiovascular Development and Disease iPSC-derived cardiomyocytes human iPSC sarcomere development sarcomere disassembly transfection efficiency non-viral vector incorporation |
title | Sarcomere Disassembly and Transfection Efficiency in Proliferating Human iPSC-Derived Cardiomyocytes |
title_full | Sarcomere Disassembly and Transfection Efficiency in Proliferating Human iPSC-Derived Cardiomyocytes |
title_fullStr | Sarcomere Disassembly and Transfection Efficiency in Proliferating Human iPSC-Derived Cardiomyocytes |
title_full_unstemmed | Sarcomere Disassembly and Transfection Efficiency in Proliferating Human iPSC-Derived Cardiomyocytes |
title_short | Sarcomere Disassembly and Transfection Efficiency in Proliferating Human iPSC-Derived Cardiomyocytes |
title_sort | sarcomere disassembly and transfection efficiency in proliferating human ipsc derived cardiomyocytes |
topic | iPSC-derived cardiomyocytes human iPSC sarcomere development sarcomere disassembly transfection efficiency non-viral vector incorporation |
url | https://www.mdpi.com/2308-3425/9/2/43 |
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