Mammalian heart renewal by pre-existing cardiomyocytes
Open accessAbstract
Although recent studies have revealed that heart cells are generated in adult mammals, the frequency of generation and the source of new heart cells are not yet known. Some studies suggest a high rate of stem cell activity with differentiation of progenitors to cardiomyocytes. Other studies suggest that new cardiomyocytes are born at a very low rate, and that they may be derived from the division of pre-existing cardiomyocytes. Here we show, by combining two different pulse-chase approaches--genetic fate-mapping with stable isotope labelling, and multi-isotope imaging mass spectrometry--that the genesis of cardiomyocytes occurs at a low rate by the division of pre-existing cardiomyocytes during normal ageing, a process that increases adjacent to areas of myocardial injury. We found that cell cycle activity during normal ageing and after injury led to polyploidy and multinucleation, but also to new diploid, mononucleate cardiomyocytes. These data reveal pre-existing cardiomyocytes as the dominant source of cardiomyocyte replacement in normal mammalian myocardial homeostasis as well as after myocardial injury.
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There is emerging evidence for a cardiac stem cell population that may engage in limited regeneration in addition to low-rate renewal of preexisting cardiomyocytes.
“There is emerging evidence supporting the existence of a cardiac stem cell population that may engage in some limited regeneration processes (32) in addition to a low rate renewal of preexisting cardiomyocytes (119).”
From The Hippo signal transduction network for exercise physiologists (2016) · cites this paper as [119]
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- Authors
- Senyo, S. E., Steinhauser, M. L., Pizzimenti, C. L., Yang, V. K., Cai, L., Wang, M., Wu, T.-D., Guerquin-Kern, J.-L., Lechene, C. P., & Lee, R. T.
- Affiliations
- Brigham and Women's Hospital (US)
- Inserm (FR)
- Corresponding author
- Lee, Richard T.
- Venue
- Nature
- Published
- 2012-12-05
- Volume
- 493
- Issue
- 7432
- Pages
- 433-436
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC3548046
- OpenAlex
- W2093494581
- Cited by
- 1,343
- References
- 29
- Citations by year
- 2026: 36 · 2025: 57 · 2024: 87 · 2023: 75 · 2022: 89 · 2021: 115 · 2020: 112 · 2019: 100 · 2018: 110 · 2017: 120 · 2016: 107 · 2015: 121 · 2014: 126 · 2013: 80 · 2012: 4
- FWCI
- 42.52
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Digital Access to Scholarship at Harvard (DASH) (Harvard University) (submittedVersion, cc-by)
- RePEc: Research Papers in Economics (submittedVersion)
- Funders
- National Institute on Aging (AG040019, R01AG032977, AG032977, R21AG034641, R01AG040019, AG034641)
- National Heart, Lung, and Blood Institute (F32HL108570)
- National Institute of Diabetes and Digestive and Kidney Diseases (K08DK090147)
- National Institute of Biomedical Imaging and Bioengineering (EB001974, P20EB001974, P41EB001974)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Congenital heart defects research
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Health Sciences › Medicine › Genetics › Mesenchymal stem cell research
- Keywords
- cardiomyocyte turnover, myocardial infarction, cardiomyocyte proliferation, genetic fate mapping, polyploidy, multinucleation, cell cycle activity, cardiac regeneration
- MeSH terms
- Aging, Animals, Cell Cycle, DNA, Female, Heart, Homeostasis, Isotope Labeling, Male, Mammals, Myocardial Infarction, Myocardium, Polyploidy, Regeneration, Mass Spectrometry, Myocytes, Cardiac, Myoblasts, Cardiac, Mice
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