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Cited by 4Pluripotent Stem Cells ResearchCardiac electrophysiology and arrhythmiasCongenital heart defects research

Gene Expression, Morphology, and Electrophysiology During the Dynamic Development of Human Induced Pluripotent Stem Cell-Derived Atrial- and Ventricular-Like Cardiomyocytes

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Zhou, Yafei, Zhou, Rui, Huang, Wenjun, Wang, Jie, Jiang, Congshan, Li, Anmao, Huang, Christopher, Zhang, Yanmin·2024·Biologics: Targets and Therapy
DOI 10.2147/btt.s448054PMC PMC11093124
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Abstract

Background and Objectives: Gene expression, morphology, and electrophysiological combination are essential for assessing the dynamic development of human induced pluripotent stem cell-derived atrial- and ventricular-like cardiomyocytes (iPS-AM and iPS-VM, respectively). Methods: For iPS-AM/VM differentiation, we performed the small molecule-based temporal modulation of the retinoic acid and bone morphogenetic protein signaling pathways. We investigated the gene expression and morphology using immunofluorescence, quantitative real-time polymerase chain reaction, flow cytometry, and transmission electron microscopy as well as registered electrophysiological functions using a whole-cell patch clamp on days 20, 30, and 60 post-differentiations. Results: Pan-cardiomyocyte marker, including troponin T2 ( TNNT2 ) and alpha-actinin-2 ( ACTN2 ), expressions increased both in iPS-AMs and iPS-VMs. Similarly, the mRNA expression of both iPS-AM-specific markers, ie, natriuretic peptide A ( NPPA ), myosin light chain 7 ( MYL7 ), and K+ channel Kir3.4 ( KCNJ5 ), and iPS-VM-specific markers, ie, gap junction α-1 ( GJA1 ), myosin light chain 2 ( MYL2 ), and alpha-1-subunit of a voltage-dependent L-type calcium channel ( CACNA1C ), increased from 0 to 20 days, and then decreased from 30 to 60 days. Concerning morphology, cardiac troponin-T (cTnT) arrangement was progressively organized and developed from a disorderly myofibrillar distribution to an organized sarcomere pattern both in iPS-AMs and iPS-VMs. Mitochondrial numbers gradually increased and those of lipid droplets decreased during dynamic development. Regarding physiological function, the resting and action potential amplitudes remained statistically indifferent in both cell types, and the action potential duration was prolonged during the development. Conclusion: IPS-AMs/VMs displayed dynamic development concerning their gene expression, morphology, and electrophysiological function. The discoveries of this study could provide novel insights into heart development and encourage further research. Keywords: cardiomyocytes, induced pluripotent stem cells, dynamic development, gene expression, morphology, action potential

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Cited by

Sorted by citations

Authors
Zhou, Y., Zhou, R., Huang, W., Wang, J., Jiang, C., Li, A., Huang, C., & Zhang, Y.
Affiliations
  • Xi’an Children’s Hospital (CN)
  • University of Cambridge (GB)
Corresponding author
Zhang, Yanmin
ORCID
Venue
Biologics: Targets and Therapy
Publisher
Informa UK Limited
Published
2024-05
Volume
Volume 18
Pages
115-127
ISSN
  • 1177-5475 (ISSN-L)
  • 1177-5491
DOI
10.2147/btt.s448054
PMC
PMC11093124
OpenAlex
W4396810698
Cited by
4
References
3
Citations by year
2026: 1 · 2025: 2 · 2024: 1
FWCI
0.54
Type
journal article
Language
en
Open access
Licence
Locations
  • Biologics (publishedVersion, cc-by-nc)
  • PubMed Central (publishedVersion, cc-by-nc)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • Dove Medical Press (Taylor and Francis Group) (submittedVersion, cc-by-nc)
Funders
  • National Natural Science Foundation of China (82211530115, 81974014)
  • Natural Science Foundation of Shaanxi Province (2022JQ-968, 2021JQ-024, 2022JQ, 2022JQ-877)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pluripotent Stem Cells Research
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac electrophysiology and arrhythmias
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Congenital heart defects research
Keywords
iPSC-derived cardiomyocytes, cardiomyocyte differentiation, retinoic acid signaling, BMP signaling, small molecule modulation, cardiac gene expression, sarcomere organization, myofibrils, mitochondrial number, lipid droplets, action potential duration, electrophysiological function, heart development

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