Somatic_mutations_in_UV_exposed_mouse_skin_-sc-4751
Somatic_mutations_in_UV_exposed_mouse_skin_
Tracking the behaviour of p53 mutant progenitors demonstrated their competitive advantage over wild type cells. This behavior can be temporarily promoted by the exposure to physiological dose of UV. However  long term treatment resulted in a striking reduction in the proportion of p53 mutant cells which were desplaced by UV induced mutations with higher competitive fittness. We aim to test the hypothesis that mutaions in drivers of clonal expansion will be present in the UV-treated epiderm but not in adjacent unexposed skin.
Aging human tissues such as sun exposed epidermis harbour numerous somatic mutant clones, but how they establish and persist is unknown.  Here, we tracked the behavior of single p53R245W/wt mutant (p53*) progenitors in normal mouse epidermis.  Initially, p53* progenitors colonised the tissue due to their fate being imbalanced in favour of proliferation.  Those mutant cells that did differentiate were retained in the epidermis due to a defect in shedding.  Subsequently, the p53* phenotype became attenuated allowing the partly mutated epidermis to establish a new steady state. Exposure to physiological doses of ultraviolet (UV) light initially promoted the expansion of the p53* population.  However, long term UV treatment  resulted in a striking reduction in the proportion of p53* cells which were displaced by UV induced mutants with higher competitive fitness.  We conclude that phenotypic adaptation and cell competition restrain p53 mutant progenitors, enabling tissue integrity to be maintained.