Cell competition in heart development and homeostasis

Tesis doctoral inédita leída en la Universidad Autónoma de Madrid, Facultad de Ciencias, Departamento de Biología Molecular. Fecha de lectura: 30-01-2015Heterogeneous 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 embryo- nic cells. Here we show that cell competition can be efficiently induced in mouse cardiomyocytes by mosaic overexpression of Myc both during gestation and adult life. The expansion of the Myc-overexpressing cardiomyocyte population is driven by the elimination of wild type cardiomyocytes, which happens through apoptosis in the embryonic heart and autophagic cell death in the adult cardiomyocytes. Importantly, this cardiomyocyte replacement is phenotypically silent and does not affect heart anatomy or function. Myc overexpression in the adult heart induces a cardioprotective response through the reactivation of fetal programs. Moreover, cell competition induction in the epicardium during development shows an increased contribution of this lineage to cardiac myocytes. These results show that 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