title: Cell competition promotes phenotypically silent cardiomyocyte replacement in the mammalian heart.
abstract: Heterogeneous anabolic capacity in cell populations can trigger a phenomenon known as cell competition, through which less active cells are eliminated. Cell competition has been induced experimentally in stem/precursor cell populations in insects and mammals and takes place endogenously in early mouse embryonic cells. Here, we show that cell competition can be efficiently induced in mouse cardiomyocytes by mosaic overexpression of Myc during both gestation and adult life. The expansion of the Myc-overexpressing cardiomyocyte population is driven by the elimination of wild-type cardiomyocytes. Importantly, this cardiomyocyte replacement is phenotypically silent and does not affect heart anatomy or function. These results show that the capacity for cell competition in mammals is not restricted to stem cell populations and suggest that stimulated cell competition has potential as a cardiomyocyte-replacement strategy.
authors.affiliation: Departamento de Desarrollo y Reparación Cardiovascular, Centro Nacional de Investigaciones Cardiovasculares (CNIC), c/ Melchor Fernández Almagro, 3, E-28029 Madrid, Spain.
authors.forename: Cristina
authors.initials: C
authors.lastname: Villa Del Campo
authors.affiliation: Departamento de Desarrollo y Reparación Cardiovascular, Centro Nacional de Investigaciones Cardiovasculares (CNIC), c/ Melchor Fernández Almagro, 3, E-28029 Madrid, Spain.
authors.forename: Cristina
authors.initials: C
authors.lastname: Clavería
authors.affiliation: Departamento de Desarrollo y Reparación Cardiovascular, Centro Nacional de Investigaciones Cardiovasculares (CNIC), c/ Melchor Fernández Almagro, 3, E-28029 Madrid, Spain.
authors.forename: Rocío
authors.initials: R
authors.lastname: Sierra
authors.affiliation: Departamento de Desarrollo y Reparación Cardiovascular, Centro Nacional de Investigaciones Cardiovasculares (CNIC), c/ Melchor Fernández Almagro, 3, E-28029 Madrid, Spain. Electronic address: mtorres@cnic.es.
authors.forename: Miguel
authors.initials: M
authors.lastname: Torres
mesh_terms: D000818:Animals; D017209:Apoptosis; D004622:Embryo, Mammalian / Q000378:metabolism; D005260:Female; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006321:Heart / Q000033:anatomy & histology / Q000254:growth & development / Q000502:physiology*; D000072576:Homeobox Protein Nkx-2.5; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D019426:Integrases / Q000235:genetics / Q000378:metabolism; D060850:LIM-Homeodomain Proteins / Q000378:metabolism; D008297:Male; D051379:Mice; D032383:Myocytes, Cardiac / Q000166:cytology* / Q000378:metabolism; D010641:Phenotype; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000378:metabolism; D011995:Recombination, Genetic; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
chemical_list: D000072576:Homeobox Protein Nkx-2.5; D018398:Homeodomain Proteins; D060850:LIM-Homeodomain Proteins; C484469:Nkx2-5 protein, mouse; D016271:Proto-Oncogene Proteins c-myc; D014157:Transcription Factors; C485184:enhanced green fluorescent protein; C063843:insulin gene enhancer binding protein Isl-1; D049452:Green Fluorescent Proteins; C045073:Cre recombinase; D019426:Integrases