start-ver=1.4
cd-journal=joma
no-vol=16
cd-vols=
no-issue=1
article-no=
start-page=519
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2025
dt-pub=20250926
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Specific induction of right ventricular-like cardiomyocytes from human pluripotent stem cells
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Background Applications employing human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) require well-characterized, chamber-specific hPSC-CMs. Distinct first heart field (FHF) and second heart field (SHF) cardiac progenitor populations give rise to the left ventricular (LV) and right ventricular (RV) cardiomyocytes, respectively. This developmental difference in cardiomyocyte origin suggests that chamber-specific cardiomyocytes have unique characteristics. Therefore, efficient strategies to differentiate human pluripotent stem cells (hPSCs) specifically to LV-like or RV-like cardiomyocytes are needed and it is still unknown whether there is a phenotypic difference between LV-like cardiomyocytes and RV-like cardiomyocytes derived from hPSCs.
Methods An established hPSC cardiac differentiation protocol employing sequential GSK3β inhibition followed by Wnt inhibition (GiWi) was modified by addition of insulin or BMP antagonists during mesoderm formation. Cardiac progenitor populations were evaluated for FHF and SHF markers, and differentiated hPSC-CMs were characterized for chamber-specific markers.
Results The GiWi protocol produced mainly FHF-like progenitor cells that gave rise to LV-like cardiomyocytes. Inhibition of endogenous BMP signaling during mesoderm induction using insulin or BMP antagonists reduced expression of FHF markers and increased expression of SHF markers in cardiac progenitor cells. hPSC-CMs arising from the SHF-like progenitor cells showed an RV-like gene expression pattern and exhibited phenotypic differences in spontaneous contraction rate, Ca2+ transients, and cell size compared to control LV-like cardiomyocytes.
Conclusion This study establishes methodology to generate RV-like hPSC-CMs to support the development of disease modeling research using chamber-specific hPSC-CMs.
en-copyright=
kn-copyright=
en-aut-name=SaitoYukihiro
en-aut-sei=Saito
en-aut-mei=Yukihiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=
en-aut-name=NakamuraKazufumi
en-aut-sei=Nakamura
en-aut-mei=Kazufumi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=
en-aut-name=KatanosakaYuki
en-aut-sei=Katanosaka
en-aut-mei=Yuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=
en-aut-name=IidaToshihiro
en-aut-sei=Iida
en-aut-mei=Toshihiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=
en-aut-name=KusumotoDai
en-aut-sei=Kusumoto
en-aut-mei=Dai
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=
en-aut-name=SatoRyushi
en-aut-sei=Sato
en-aut-mei=Ryushi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=
en-aut-name=AdachiRiki
en-aut-sei=Adachi
en-aut-mei=Riki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=
en-aut-name=ShimizuSatoshi
en-aut-sei=Shimizu
en-aut-mei=Satoshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=
en-aut-name=KurokawaJunko
en-aut-sei=Kurokawa
en-aut-mei=Junko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=
en-aut-name=AkagiSatoshi
en-aut-sei=Akagi
en-aut-mei=Satoshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=
en-aut-name=YoshidaMasashi
en-aut-sei=Yoshida
en-aut-mei=Masashi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=11
ORCID=
en-aut-name=MiyoshiToru
en-aut-sei=Miyoshi
en-aut-mei=Toru
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=12
ORCID=
en-aut-name=MoritaHiroshi
en-aut-sei=Morita
en-aut-mei=Hiroshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=13
ORCID=
en-aut-name=NaruseKeiji
en-aut-sei=Naruse
en-aut-mei=Keiji
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=14
ORCID=
en-aut-name=NishidaMikako
en-aut-sei=Nishida
en-aut-mei=Mikako
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=15
ORCID=
en-aut-name=UdonoHeiichiro
en-aut-sei=Udono
en-aut-mei=Heiichiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=16
ORCID=
en-aut-name=ZhangJianhua
en-aut-sei=Zhang
en-aut-mei=Jianhua
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=17
ORCID=
en-aut-name=YuasaShinsuke
en-aut-sei=Yuasa
en-aut-mei=Shinsuke
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=18
ORCID=
en-aut-name=KampTimothy J.
en-aut-sei=Kamp
en-aut-mei=Timothy J.
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=19
ORCID=
en-aut-name=ItoHiroshi
en-aut-sei=Ito
en-aut-mei=Hiroshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=20
ORCID=
affil-num=1
en-affil=Department of Cardiovascular Medicine, Okayama University Hospital
kn-affil=
affil-num=2
en-affil=Department of Cardiovascular Medicine, Okayama University Hospital
kn-affil=
affil-num=3
en-affil=Department of Cardiovascular Physiology, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=4
en-affil=Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=5
en-affil=Department of Biomedical Informatics and Molecular Biology, The Sakaguchi Laboratory, Keio University School of Medicine
kn-affil=
affil-num=6
en-affil=Department of Bio-Informational Pharmacology, School of Pharmaceutical Sciences, University of Shizuoka
kn-affil=
affil-num=7
en-affil=Department of Bio-Informational Pharmacology, School of Pharmaceutical Sciences, University of Shizuoka
kn-affil=
affil-num=8
en-affil=Department of Bio-Informational Pharmacology, School of Pharmaceutical Sciences, University of Shizuoka
kn-affil=
affil-num=9
en-affil=Department of Bio-Informational Pharmacology, School of Pharmaceutical Sciences, University of Shizuoka
kn-affil=
affil-num=10
en-affil=Department of Cardiovascular Medicine, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=11
en-affil=Department of Chronic Kidney Disease and Cardiovascular Disease, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=12
en-affil=Department of Cardiovascular Medicine, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=13
en-affil=Department of Cardiovascular Therapeutics, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=14
en-affil=Department of Cardiovascular Physiology, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=15
en-affil=Department of Metabolic Immune Regulation, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=16
en-affil=Department of Metabolic Immune Regulation, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=17
en-affil=Department of Medicine, University of Wisconsin School of Medicine and Public Health
kn-affil=
affil-num=18
en-affil=Department of Cardiovascular Medicine, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=19
en-affil=Department of Medicine, University of Wisconsin School of Medicine and Public Health
kn-affil=
affil-num=20
en-affil=Department of Cardiovascular Medicine, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
en-keyword=Human pluripotent stem cell-derived cardiomyocytes
kn-keyword=Human pluripotent stem cell-derived cardiomyocytes
en-keyword=Anterior second heart field
kn-keyword=Anterior second heart field
en-keyword=Right ventricle
kn-keyword=Right ventricle
en-keyword=Bone morphogenetic protein
kn-keyword=Bone morphogenetic protein
END
start-ver=1.4
cd-journal=joma
no-vol=10
cd-vols=
no-issue=
article-no=
start-page=5754
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2019
dt-pub=20191217
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Elimination of fukutin reveals cellular and molecular pathomechanisms in muscular dystrophy-associated heart failure
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Heart failure is the major cause of death for muscular dystrophy patients, however, the molecular pathomechanism remains unknown. Here, we show the detailed molecular pathogenesis of muscular dystrophy-associated cardiomyopathy in mice lacking the fukutin gene (Fktn), the causative gene for Fukuyama muscular dystrophy. Although cardiac Fktn elimination markedly reduced alpha-dystroglycan glycosylation and dystrophin-glycoprotein complex proteins in sarcolemma at all developmental stages, cardiac dysfunction was observed only in later adulthood, suggesting that membrane fragility is not the sole etiology of cardiac dysfunction. During young adulthood, Fktn-deficient mice were vulnerable to pathological hypertrophic stress with downregulation of Akt and the MEF2-histone deacetylase axis. Acute Fktn elimination caused severe cardiac dysfunction and accelerated mortality with myocyte contractile dysfunction and disordered Golgi-microtubule networks, which were ameliorated with colchicine treatment. These data reveal fukutin is crucial for maintaining myocyte physiology to prevent heart failure, and thus, the results may lead to strategies for therapeutic intervention.
en-copyright=
kn-copyright=
en-aut-name=UjiharaYoshihiro
en-aut-sei=Ujihara
en-aut-mei=Yoshihiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=
en-aut-name=KanagawaMotoi
en-aut-sei=Kanagawa
en-aut-mei=Motoi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=
en-aut-name=MohriSatoshi
en-aut-sei=Mohri
en-aut-mei=Satoshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=
en-aut-name=TakatsuSatomi
en-aut-sei=Takatsu
en-aut-mei=Satomi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=
en-aut-name=KobayashiKazuhiro
en-aut-sei=Kobayashi
en-aut-mei=Kazuhiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=
en-aut-name=TodaTatsushi
en-aut-sei=Toda
en-aut-mei=Tatsushi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=
en-aut-name=NaruseKeiji
en-aut-sei=Naruse
en-aut-mei=Keiji
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=
en-aut-name=KatanosakaYuki
en-aut-sei=Katanosaka
en-aut-mei=Yuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=
affil-num=1
en-affil=Department of Cardiovascular Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=
affil-num=2
en-affil=Division of Neurology/Molecular Brain Science, Kobe University Graduate School of Medicine
kn-affil=
affil-num=3
en-affil=Department of Cardiovascular Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=
affil-num=4
en-affil=Department of Cardiovascular Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=
affil-num=5
en-affil=Division of Neurology/Molecular Brain Science, Kobe University Graduate School of Medicine
kn-affil=
affil-num=6
en-affil=Division of Neurology/Molecular Brain Science, Kobe University Graduate School of Medicine
kn-affil=
affil-num=7
en-affil=Department of Cardiovascular Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=
affil-num=8
en-affil=Department of Cardiovascular Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=
END
start-ver=1.4
cd-journal=joma
no-vol=5
cd-vols=
no-issue=
article-no=
start-page=3932
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2014
dt-pub=20140529
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=TRPV2 is critical for the maintenance of cardiac structure and function in mice
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=The heart has a dynamic compensatory mechanism for haemodynamic stress. However, the molecular details of how mechanical forces are transduced in the heart are unclear. Here we show that the transient receptor potential, vanilloid family type 2 (TRPV2) cation channel is critical for the maintenance of cardiac structure and function. Within 4 days of eliminating TRPV2 from hearts of the adult mice, cardiac function declines severely, with disorganization of the intercalated discs that support mechanical coupling with neighbouring myocytes and myocardial conduction defects. After 9 days, cell shortening and Ca2+ handling by single myocytes are impaired in TRPV2-deficient hearts. TRPV2-deficient neonatal cardiomyocytes form no intercalated discs and show no extracellular Ca2+-dependent intracellular Ca2+ increase and insulin-like growth factor (IGF-1) secretion in response to stretch stimulation. We further demonstrate that IGF-1 receptor/PI3K/Akt pathway signalling is significantly downregulated in TRPV2-deficient hearts, and that IGF-1 administration partially prevents chamber dilation and impairment in cardiac pump function in these hearts. Our results improve our understanding of the molecular processes underlying the maintenance of cardiac structure and function.
en-copyright=
kn-copyright=
en-aut-name=KatanosakaYuki
en-aut-sei=Katanosaka
en-aut-mei=Yuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=
en-aut-name=IwasakiKeiichiro
en-aut-sei=Iwasaki
en-aut-mei=Keiichiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=
en-aut-name=UjiharaYoshihiro
en-aut-sei=Ujihara
en-aut-mei=Yoshihiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=
en-aut-name=TakatsuSatomi
en-aut-sei=Takatsu
en-aut-mei=Satomi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=
en-aut-name=NishitsujiKoki
en-aut-sei=Nishitsuji
en-aut-mei=Koki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=
en-aut-name=KanagawaMotoi
en-aut-sei=Kanagawa
en-aut-mei=Motoi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=
en-aut-name=SudoAtsushi
en-aut-sei=Sudo
en-aut-mei=Atsushi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=
en-aut-name=TodaTatsushi
en-aut-sei=Toda
en-aut-mei=Tatsushi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=
en-aut-name=KatanosakaKimiaki
en-aut-sei=Katanosaka
en-aut-mei=Kimiaki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=
en-aut-name=MohriSatoshi
en-aut-sei=Mohri
en-aut-mei=Satoshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=
en-aut-name=NaruseKeiji
en-aut-sei=Naruse
en-aut-mei=Keiji
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=11
ORCID=
affil-num=1
en-affil=
kn-affil=Department of Cardiovascular Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
affil-num=2
en-affil=
kn-affil=Department of Cardiovascular Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
affil-num=3
en-affil=
kn-affil=Department of Cardiovascular Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
affil-num=4
en-affil=
kn-affil=Department of Cardiovascular Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
affil-num=5
en-affil=
kn-affil=Department of Cardiovascular Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
affil-num=6
en-affil=
kn-affil=Division of Neurology/Molecular Brain Science, Kobe University Graduate School of Medicine
affil-num=7
en-affil=
kn-affil=Division of Neurology/Molecular Brain Science, Kobe University Graduate School of Medicine
affil-num=8
en-affil=
kn-affil=Division of Neurology/Molecular Brain Science, Kobe University Graduate School of Medicine
affil-num=9
en-affil=
kn-affil=Department of Neuroscience II, Research Institute of Environmental Medicine, Nagoya University
affil-num=10
en-affil=
kn-affil=Department of Cardiovascular Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
affil-num=11
en-affil=
kn-affil=Department of Cardiovascular Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
END
start-ver=1.4
cd-journal=joma
no-vol=4
cd-vols=
no-issue=
article-no=
start-page=
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2014
dt-pub=201412
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Cardiac mechanosensitive integrator
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=
en-copyright=
kn-copyright=
en-aut-name=KatanosakaYuki
en-aut-sei=Katanosaka
en-aut-mei=Yuki
kn-aut-name=片野坂友紀
kn-aut-sei=片野坂
kn-aut-mei=友紀
aut-affil-num=1
ORCID=
affil-num=1
en-affil=
kn-affil=Department of Medicine and Clinical Sciences, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
END