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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.

Pubmed ID: 20362536

Authors

  • Bondar T
  • Medzhitov R

Journal

Cell stem cell

Publication Data

April 2, 2010

Associated Grants

  • Agency: NIDDK NIH HHS, Id: P30 DK072442
  • Agency: NIAID NIH HHS, Id: R01 AI046688
  • Agency: NIAID NIH HHS, Id: R01 AI046688-05
  • Agency: NIAID NIH HHS, Id: R01 AI055502
  • Agency: NIAID NIH HHS, Id: R01 AI055502-05
  • Agency: NIDDK NIH HHS, Id: R01 DK071754
  • Agency: NIDDK NIH HHS, Id: R01 DK071754-04
  • Agency: Howard Hughes Medical Institute, Id:

Mesh Terms

  • Animals
  • Apoptosis
  • Cell Aging
  • Cell Communication
  • Cell Proliferation
  • Clone Cells
  • DNA Damage
  • Gene Expression Profiling
  • Gene Expression Regulation, Developmental
  • Genes, Dominant
  • Hematopoietic Stem Cells
  • Mice
  • Models, Biological
  • Mutation
  • Phenotype
  • Radiation, Ionizing
  • Stress, Physiological
  • Tumor Suppressor Protein p53