Cell competition promotes phenotypically silent cardiomyocyte replacement in the mammalian heart

Cristina Villa Del Campo; Cristina Clavería; Rocío Sierra; Miguel Torres

doi:10.1016/j.celrep.2014.08.005

Cell competition promotes phenotypically silent cardiomyocyte replacement in the mammalian heart

Cell Rep. 2014 Sep 25;8(6):1741-1751. doi: 10.1016/j.celrep.2014.08.005. Epub 2014 Sep 4.

Authors

Cristina Villa Del Campo¹, Cristina Clavería¹, Rocío Sierra¹, Miguel Torres²

Affiliations

¹ Departamento de Desarrollo y Reparación Cardiovascular, Centro Nacional de Investigaciones Cardiovasculares (CNIC), c/ Melchor Fernández Almagro, 3, E-28029 Madrid, Spain.
² 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.

PMID: 25199831
DOI: 10.1016/j.celrep.2014.08.005

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Apoptosis
Embryo, Mammalian / metabolism
Female
Green Fluorescent Proteins / genetics
Green Fluorescent Proteins / metabolism
Heart / anatomy & histology
Heart / growth & development
Heart / physiology*
Homeobox Protein Nkx-2.5
Homeodomain Proteins / genetics
Homeodomain Proteins / metabolism
Integrases / genetics
Integrases / metabolism
LIM-Homeodomain Proteins / metabolism
Male
Mice
Myocytes, Cardiac / cytology*
Myocytes, Cardiac / metabolism
Phenotype
Proto-Oncogene Proteins c-myc / genetics
Proto-Oncogene Proteins c-myc / metabolism
Recombination, Genetic
Stem Cells / cytology
Stem Cells / metabolism
Transcription Factors / genetics
Transcription Factors / metabolism

Substances

Homeobox Protein Nkx-2.5
Homeodomain Proteins
LIM-Homeodomain Proteins
Nkx2-5 protein, mouse
Proto-Oncogene Proteins c-myc
Transcription Factors
enhanced green fluorescent protein
insulin gene enhancer binding protein Isl-1
Green Fluorescent Proteins
Cre recombinase
Integrases

Associated data

GEO/GSE58858