title: c-kit+ cells minimally contribute cardiomyocytes to the heart.
abstract: If and how the heart regenerates after an injury event is highly debated. c-kit-expressing cardiac progenitor cells have been reported as the primary source for generation of new myocardium after injury. Here we generated two genetic approaches in mice to examine whether endogenous c-kit(+) cells contribute differentiated cardiomyocytes to the heart during development, with ageing or after injury in adulthood. A complementary DNA encoding either Cre recombinase or a tamoxifen-inducible MerCreMer chimaeric protein was targeted to the Kit locus in mice and then bred with reporter lines to permanently mark cell lineage. Endogenous c-kit(+) cells did produce new cardiomyocytes within the heart, although at a percentage of approximately 0.03 or less, and if a preponderance towards cellular fusion is considered, the percentage falls to below approximately 0.008. By contrast, c-kit(+) cells amply generated cardiac endothelial cells. Thus, endogenous c-kit(+) cells can generate cardiomyocytes within the heart, although probably at a functionally insignificant level.
authors.affiliation: 1] Department of Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio 45229, USA [2] Department of Medicine, division of Cardiology, Lillehei Heart Institute, University of Minnesota, Minneapolis, Minnesota 55455, USA [3].
authors.forename: Jop H
authors.initials: JH
authors.lastname: van Berlo
authors.affiliation: 1] Department of Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio 45229, USA [2].
authors.forename: Onur
authors.initials: O
authors.lastname: Kanisicak
authors.affiliation: Department of Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio 45229, USA.
authors.forename: Marjorie
authors.initials: M
authors.lastname: Maillet
authors.affiliation: Department of Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio 45229, USA.
authors.forename: Ronald J
authors.initials: RJ
authors.lastname: Vagnozzi
authors.affiliation: Department of Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio 45229, USA.
authors.forename: Jason
authors.initials: J
authors.lastname: Karch
authors.affiliation: Department of Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio 45229, USA.
authors.forename: Suh-Chin J
authors.initials: SC
authors.lastname: Lin
authors.affiliation: Cedars-Sinai Heart Institute, 8700 Beverly Boulevard, Los Angeles, California 90048, USA.
authors.forename: Ryan C
authors.initials: RC
authors.lastname: Middleton
authors.affiliation: Cedars-Sinai Heart Institute, 8700 Beverly Boulevard, Los Angeles, California 90048, USA.
authors.forename: Eduardo
authors.initials: E
authors.lastname: Marbán
authors.affiliation: 1] Department of Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio 45229, USA [2] Howard Hughes Medical Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio 45229, USA.
authors.forename: Jeffery D
authors.initials: JD
authors.lastname: Molkentin
mesh_terms: D000375:Aging / Q000502:physiology; D000818:Animals; D002454:Cell Differentiation; D002459:Cell Fusion; D019070:Cell Lineage; D042783:Endothelial Cells / Q000166:cytology / Q000378:metabolism; D005260:Female; D006321:Heart / Q000254:growth & development; D006335:Heart Injuries / Q000473:pathology*; D019426:Integrases / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D008954:Models, Biological; D032386:Myoblasts, Cardiac / Q000166:cytology* / Q000378:metabolism*; D009206:Myocardium / Q000166:cytology*; D032383:Myocytes, Cardiac / Q000166:cytology* / Q000378:metabolism; D019009:Proto-Oncogene Proteins c-kit / Q000378:metabolism*; D012038:Regeneration / Q000502:physiology; D013629:Tamoxifen / Q000494:pharmacology
chemical_list: D013629:Tamoxifen; D019009:Proto-Oncogene Proteins c-kit; C045073:Cre recombinase; D019426:Integrases