Cooperation between cells in multicellular organisms is essential to ensure the fitness of the whole organism; however, 'cheater' mutants (which do not cooperate but benefit from the cooperation between others) can emerge, lowering fitness unless the organism can re-equilibrate towards cooperation. Here, the authors hypothesized that regulatory mechanisms operate during mammalian development to remove aberrant clones that reduce fitness. To test this, they developed a genome-wide 'cheater screen' in mouse pluripotent stem cells to identify cooperation genes, loss of which would allow cheater mutants to obtain a competitive advantage. Among the genes identified were those encoding p53, topoisomerase 1 and olfactory receptors, knockdown of which allowed mutant cells to expand disproportionately compared with wild-type cells in vitro and in vivo. Thus, these genes seem to have key roles in fostering cell cooperation in mammals.
References
Dejosez, M. et al. Safeguards for cell cooperation in mouse embryogenesis shown by genome-wide cheater screen. Science http://dx.doi.org/10.1126/science.1241628 (2013)
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David, R. Working together for the greater good. Nat Rev Mol Cell Biol 14, 688 (2013). https://doi.org/10.1038/nrm3688
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DOI: https://doi.org/10.1038/nrm3688