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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Main Authors: 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
Format: Article
Language:English
Published: MDPI AG 2022-01-01
Series:Journal of Cardiovascular Development and Disease
Subjects:
Online Access:https://www.mdpi.com/2308-3425/9/2/43
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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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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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