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Frequency of mononuclear diploid cardiomyocytes underlies natural variation in heart regeneration

Nature genetics, 2017-09, Vol.49 (9), p.1346-1353 [Peer Reviewed Journal]

COPYRIGHT 2017 Nature Publishing Group ;COPYRIGHT 2017 Nature Publishing Group ;Copyright Nature Publishing Group Sep 2017 ;ISSN: 1061-4036 ;EISSN: 1546-1718 ;DOI: 10.1038/ng.3929 ;PMID: 28783163

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Title:
Frequency of mononuclear diploid cardiomyocytes underlies natural variation in heart regeneration
Author: Patterson, Michaela ; Barske, Lindsey ; Van Handel, Ben ; Rau, Christoph D ; Gan, Peiheng ; Sharma, Avneesh ; Parikh, Shan ; Denholtz, Matt ; Huang, Ying ; Yamaguchi, Yukiko ; Shen, Hua ; Allayee, Hooman ; Crump, J Gage ; Force, Thomas I ; Lien, Ching-Ling ; Makita, Takako ; Lusis, Aldons J ; Kumar, S Ram ; Sucov, Henry M
Subjects: Animals ; Animals, Genetically Modified ; Cardiomyocytes ; Cardiomyopathy ; Cells, Cultured ; Coronary artery ; Coronary vessels ; Diploidy ; Gene Expression Profiling - methods ; Genes ; Genetic aspects ; Genetic variation ; Genomes ; Heart ; Heart - physiology ; Heart attacks ; Heart cells ; Immunoblotting ; In Situ Hybridization, Fluorescence ; Inbreeding ; Injuries ; Kinases ; Mammals ; Mice, Inbred C57BL ; Mice, Knockout ; Mice, Transgenic ; Microscopy, Confocal ; Myocardium - cytology ; Myocardium - metabolism ; Myocytes, Cardiac - cytology ; Myocytes, Cardiac - metabolism ; Physiological aspects ; Polyploidy ; Protein Kinases - genetics ; Protein Kinases - metabolism ; Protein Serine-Threonine Kinases ; Recovery of function ; Regeneration ; Regeneration (Biology) ; Regeneration - genetics ; Regeneration - physiology ; Rodents ; Stem cells ; Studies ; Surveys ; Zebrafish ; Zebrafish - genetics ; Zebrafish - metabolism
Is Part Of: Nature genetics, 2017-09, Vol.49 (9), p.1346-1353
Description: 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.
Publisher: United States: Nature Publishing Group
Language: English
Identifier: ISSN: 1061-4036
EISSN: 1546-1718
DOI: 10.1038/ng.3929
PMID: 28783163
Source: Freely Accessible Journals
MEDLINE
ProQuest Central

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Frequency of mononuclear diploid cardiomyocytes underlies natural variation in heart regeneration

COPYRIGHT 2017 Nature Publishing Group ;COPYRIGHT 2017 Nature Publishing Group ;Copyright Nature Publishing Group Sep 2017 ;ISSN: 1061-4036 ;EISSN: 1546-1718 ;DOI: 10.1038/ng.3929 ;PMID: 28783163

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