p53-mediated hematopoietic stem and progenitor cell competition.
Cell competition was originally described in Drosophila as a process for selection of the fittest cells. It is likely to play an important role in tissue homeostasis in all metazoans, but little is known about its role and regulation in mammals. By using genetic mosaic mouse models and bone marrow chimeras, we describe here a form of cell competition that selects for the least damaged cells. This competition is controlled by p53 but is distinct from the classical p53-mediated DNA damage response: it persists for months, is specific to the hematopoietic stem and progenitor cells, and depends on the relative rather than absolute level of p53 in competing cells. The competition appears to be mediated by a non-cell-autonomous induction of growth arrest and senescence-related gene expression in outcompeted cells with higher p53 activity. p53-mediated cell competition of this type could potentially contribute to the clonal expansion of incipient cancer cells.
Bondar
Tanya
T
Howard Hughes Medical Institute and Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06510, USA.
Medzhitov
Ruslan
R
Howard Hughes Medical Institute and Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06510, USA. Electronic address: ruslan.medzhitov@yale.edu.
D000818:Animals; D017209:Apoptosis / Q000528:radiation effects; D002450:Cell Communication / Q000528:radiation effects; D049109:Cell Proliferation / Q000528:radiation effects; D016922:Cellular Senescence / Q000528:radiation effects; D002999:Clone Cells; D004249:DNA Damage; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental / Q000528:radiation effects; D005799:Genes, Dominant / Q000235:genetics; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000378:metabolism* / Q000528:radiation effects; D051379:Mice; D008954:Models, Biological; D009154:Mutation / Q000235:genetics; D010641:Phenotype; D011839:Radiation, Ionizing; D013312:Stress, Physiological / Q000235:genetics / Q000528:radiation effects; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*
D016159:Tumor Suppressor Protein p53