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Frequency of mononuclear diploid cardiomyocytes underlies natural variation in heart regeneration.
- Source :
-
Nature genetics [Nat Genet] 2017 Sep; Vol. 49 (9), pp. 1346-1353. Date of Electronic Publication: 2017 Aug 07. - Publication Year :
- 2017
-
Abstract
- Adult mammalian cardiomyocyte regeneration after injury is thought to be minimal. Mononuclear diploid cardiomyocytes (MNDCMs), a relatively small subpopulation in the adult heart, may account for the observed degree of regeneration, but this has not been tested. We surveyed 120 inbred mouse strains and found that the frequency of adult mononuclear cardiomyocytes was surprisingly variable (>7-fold). Cardiomyocyte proliferation and heart functional recovery after coronary artery ligation both correlated with pre-injury MNDCM content. Using genome-wide association, we identified Tnni3k as one gene that influences variation in this composition and demonstrated that Tnni3k knockout resulted in elevated MNDCM content and increased cardiomyocyte proliferation after injury. Reciprocally, overexpression of Tnni3k in zebrafish promoted cardiomyocyte polyploidization and compromised heart regeneration. Our results corroborate the relevance of MNDCMs in heart regeneration. Moreover, they imply that intrinsic heart regeneration is not limited nor uniform in all individuals, but rather is a variable trait influenced by multiple genes.
- Subjects :
- Animals
Animals, Genetically Modified
Cells, Cultured
Gene Expression Profiling methods
Immunoblotting
In Situ Hybridization, Fluorescence
Mice, Inbred C57BL
Mice, Knockout
Mice, Transgenic
Microscopy, Confocal
Myocardium cytology
Myocytes, Cardiac cytology
Protein Kinases genetics
Protein Kinases metabolism
Protein Serine-Threonine Kinases
Regeneration genetics
Zebrafish genetics
Zebrafish metabolism
Diploidy
Heart physiology
Myocardium metabolism
Myocytes, Cardiac metabolism
Regeneration physiology
Subjects
Details
- Language :
- English
- ISSN :
- 1546-1718
- Volume :
- 49
- Issue :
- 9
- Database :
- MEDLINE
- Journal :
- Nature genetics
- Publication Type :
- Academic Journal
- Accession number :
- 28783163
- Full Text :
- https://doi.org/10.1038/ng.3929