title: Myc overexpression enhances of epicardial contribution to the developing heart and promotes extensive expansion of the cardiomyocyte population.
abstract: Myc is an essential regulator of cell growth and proliferation. Myc overexpression promotes the homeostatic expansion of cardiomyocyte populations by cell competition, however whether this applies to other cardiac lineages remains unknown. The epicardium contributes signals and cells to the developing and adult injured heart and exploring strategies for modulating its activity is of great interest. Using inducible genetic mosaics, we overexpressed Myc in the epicardium and determined the differential expansion of Myc-overexpressing cells with respect to their wild type counterparts. Myc-overexpressing cells overcolonized all epicardial-derived lineages and showed increased ability to invade the myocardium and populate the vasculature. We also found massive colonization of the myocardium by Wt1Cre-derived Myc-overexpressing cells, with preservation of cardiac development. Detailed analyses showed that this contribution is unlikely to derive from Cre activity in early cardiomyocytes but does not either derive from established epicardial cells, suggesting that early precursors expressing Wt1Cre originate the recombined cardiomyocytes. Myc overexpression does not modify the initial distribution of Wt1Cre-recombined cardiomyocytes, indicating that it does not stimulate the incorporation of early expressing Wt1Cre lineages to the myocardium, but differentially expands this initial population. We propose that strategies using epicardial lineages for heart repair may benefit from promoting cell competitive ability.
authors.affiliation: 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: Centro Nacional de Investigaciones Cardiovasculares (CNIC), c/Melchor Fernández Almagro, 3, E-28029 Madrid, Spain.
authors.forename: Ghislaine
authors.initials: G
authors.lastname: Lioux
authors.affiliation: Department of Animal Biology, Faculty of Science, Campus de Teatinos, University of Málaga, Málaga, Spain.|Andalusian Center for Nanomedicine and Biotechnology (BIONAND), c/Severo Ochoa n°25, 29590 Campanillas (Málaga), Spain.
authors.forename: Rita
authors.initials: R
authors.lastname: Carmona
authors.affiliation: 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: Department of Animal Biology, Faculty of Science, Campus de Teatinos, University of Málaga, Málaga, Spain.|Andalusian Center for Nanomedicine and Biotechnology (BIONAND), c/Severo Ochoa n°25, 29590 Campanillas (Málaga), Spain.
authors.forename: Ramón
authors.initials: R
authors.lastname: Muñoz-Chápuli
authors.affiliation: 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: Centro Nacional de Investigaciones Cardiovasculares (CNIC), c/Melchor Fernández Almagro, 3, E-28029 Madrid, Spain.
authors.forename: Miguel
authors.initials: M
authors.lastname: Torres
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000235:genetics; D019070:Cell Lineage / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics; D003331:Coronary Vessels / Q000254:growth & development / Q000378:metabolism / Q000473:pathology; D018507:Gene Expression Regulation, Developmental; D006321:Heart / Q000254:growth & development*; D019426:Integrases / Q000235:genetics; D051379:Mice; D009206:Myocardium / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000378:metabolism; D038081:Organogenesis / Q000235:genetics*; D010496:Pericardium / Q000254:growth & development / Q000378:metabolism; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics*
chemical_list: D016271:Proto-Oncogene Proteins c-myc; C045073:Cre recombinase; D019426:Integrases