Cardiomyocyte Maturation: New Phase in Development
Open accessAbstract
Maturation is the last phase of heart development that prepares the organ for strong, efficient, and persistent pumping throughout the mammal’s lifespan. This process is characterized by structural, gene expression, metabolic, and functional specializations in cardiomyocytes as the heart transits from fetal to adult states. Cardiomyocyte maturation gained increased attention recently due to the maturation defects in pluripotent stem cell–derived cardiomyocyte, its antagonistic effect on myocardial regeneration, and its potential contribution to cardiac disease. Here, we review the major hallmarks of ventricular cardiomyocyte maturation and summarize key regulatory mechanisms that promote and coordinate these cellular events. With advances in the technical platforms used for cardiomyocyte maturation research, we expect significant progress in the future that will deepen our understanding of this process and lead to better maturation of pluripotent stem cell–derived cardiomyocyte and novel therapeutic strategies for heart disease.
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Key genes in the maturation of fatty acid metabolism, sarcomere, and ion channels were upregulated in cardiomyocytes from hvCTS and hvCOC relative to those from CS and hvCAS.
“Key genes in the maturation of fatty acid metabolism, sarcomere, and ion channels were also upregulated in CMs from the hvCTS and hvCOC relative to those from the CS and hvCAS (Figure 3C).11,23,36”
From Single-cell RNA sequencing reveals maturation trajectory in human pluripotent stem cell-derived cardiomyocytes in engineered tissues (2023) · cites this paper as [23]
The Metabolic Maturation and Intracellular Regulation sections (page not provided) describe changes in fatty-acid metabolism, sarcomere genes, and electrophysiological genes during cardiomyocyte maturation. They do not report the claimed upregulation in hvCTS and hvCOC relative to CS and hvCAS; that specific comparison is not supported by this source. (LLM, conf=0.88)
Experimental — accuracy not yet measuredCell cycle silencing with expression of cell adhesion genes is a sign of mature cardiomyocytes.
“Cell cycle silencing with the expression of cell adhesion genes was also shown to be a sign of mature CM.23”
From Single-cell RNA sequencing reveals maturation trajectory in human pluripotent stem cell-derived cardiomyocytes in engineered tissues (2023) · cites this paper as [23]
The “Proliferation-to-hypertrophy Transition” section describes cell-cycle exit and repression of cell-cycle regulators during cardiomyocyte maturation. “CM Integration into a Mature Tissue” describes the formation of cell-adhesion junctions, but emphasizes that their components may already be expressed in immature cells and are redistributed during maturation. It does not establish expression of cell-adhesion genes itself as a sign of maturity. (LLM, conf=0.79)
Experimental — accuracy not yet measuredIn vivo cardiac developmental process can be divided into specification, morphogenesis, and maturation.
“In vivo cardiac developmental process can be divided into three processes -specification, morphogenesis, and maturation,23”
From Single-cell RNA sequencing reveals maturation trajectory in human pluripotent stem cell-derived cardiomyocytes in engineered tissues (2023) · cites this paper as [23]
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- Authors
- Guo, Y., & Pu, W. T.
- Affiliations
- Boston Children's Hospital (US)
- Corresponding author
- Pu, William T.
- Venue
- Circulation Research
- Published
- 2020-04-10
- Volume
- 126
- Issue
- 8
- Pages
- 1086-1106
- ISSN
- 0009-7330 (ISSN-L)
- 1524-4571
- PMC
- PMC7199445
- OpenAlex
- W3015790912
- Cited by
- 653
- References
- 17
- Citations by year
- 2026: 91 · 2025: 113 · 2024: 121 · 2023: 129 · 2022: 98 · 2021: 79 · 2020: 21 · 2019: 1
- FWCI
- 7.87
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- cc-by
- Locations
- Circulation Research (publishedVersion, cc-by)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Heart, Lung, and Blood Institute (UM1HL098166, R01HL146634)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Congenital heart defects research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pluripotent Stem Cells Research
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac electrophysiology and arrhythmias
- Keywords
- cardiomyocyte maturation, ventricular myocytes, fetal to adult transition, pluripotent stem cell-derived cardiomyocytes, cardiac regeneration, heart disease, cardiomyocyte metabolism, gene expression regulation, heart development
- MeSH terms
- Animals, Cell Differentiation, Heart Diseases, Humans, Myocytes, Cardiac, Pluripotent Stem Cells
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