TY - JOUR
T1 - Sarcomere Disassembly and Transfection Efficiency in Proliferating Human iPSC-Derived Cardiomyocytes
AU - Yuan, Qianliang
AU - Maas, Renee G. C.
AU - Brouwer, Ellen C. J.
AU - Pei, Jiayi
AU - Blok, Christian Snijders
AU - Popovic, Marko A.
AU - Paauw, Nanne J.
AU - Bovenschen, Niels
AU - Hjortnaes, Jesper
AU - Harakalova, Magdalena
AU - Doevendans, Pieter A.
AU - Sluijter, Joost P. G.
AU - van der Velden, Jolanda
AU - Buikema, Jan W.
N1 - Funding Information: Funding: Q.Y. is supported by the Chinese Scholarship Council (CSC) with file number 201706170068. RM is supported by a grant of the PLN Foundation. P.A.D. is supported by CUREPLaN Leducq. J.P.G.S. is supported by H2020-EVICARE (#725229) of the European Research Council (ERC). J.W.B. is supported by the UMC Utrecht Clinical Fellowship, Netherlands Heart Institute Fellowship, and CVON-Dosis young talent grant; Netherlands Heart Foundation (CVON-Dosis 2014–40). Publisher Copyright: © 2022 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2022/2/1
Y1 - 2022/2/1
N2 - 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 hiPSCCMs 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.
AB - 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 hiPSCCMs 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.
KW - Binucleation
KW - Cardiomyocyte proliferation
KW - Cardiomyocytes
KW - Human iPSC
KW - IPSC-derived cardiomyocytes
KW - M-phase
KW - Mitosis
KW - Non-viral vector incorporation
KW - Proliferation
KW - Sarcomere development
KW - Sarcomere disassembly
KW - Self-duplication
KW - Transfection efficiency
UR - http://www.scopus.com/inward/record.url?scp=85123684731&partnerID=8YFLogxK
U2 - https://doi.org/10.3390/jcdd9020043
DO - https://doi.org/10.3390/jcdd9020043
M3 - Article
C2 - 35200697
SN - 2308-3425
VL - 9
JO - Journal of cardiovascular development and disease
JF - Journal of cardiovascular development and disease
IS - 2
M1 - 43
ER -