期刊
NATURE
卷 548, 期 7667, 页码 334-+出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/nature23304
关键词
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资金
- New York Stem Cell Foundation
- Edward Mallinckrodt, Jr. Foundation
- Howard Hughes Medical Institute Scholar award
- National Institute of Arthritis and Musculoskeletal and Skin Disease, National Institutes of Health (NIH) [5R01AR063663-04, 1R01AR067755-01A1]
- NIH Predoctoral Program in Cellular and Molecular Biology [NIH T32GM007223]
- Human Genetics Training Grant [NIH T32HD001749]
- National Cancer Institute of the NIH [F31CA206419]
- James Hudson Brown - Alexander Brown Coxe Postdoctoral Fellowship
- CT Stem Cell Grant [14-SCA-YALE-05]
Cells in healthy tissues acquire mutations with surprising frequency. Many of these mutations are associated with abnormal cellular behaviours such as differentiation defects and hyperproliferation, yet fail to produce macroscopically detectable phenotypes(1-3). It is currently unclear how the tissue remains phenotypically normal, despite the presence of these mutant cells. Here we use intravital imaging to track the fate of mouse skin epithelium burdened with varying numbers of activated Wnt/beta-catenin stem cells. We show that all resulting growths that deform the skin tissue architecture regress, irrespective of their size. Wild-type cells are required for the active elimination of mutant cells from the tissue, while utilizing both endogenous and ectopic cellular behaviours to dismantle the aberrant structures. After regression, the remaining structures are either completely eliminated or converted into functional skin appendages in a niche-dependent manner. Furthermore, tissue aberrancies generated from oncogenic Hras, and even mutationin-dependent deformations to the tissue, can also be corrected, indicating that this tolerance phenomenon reflects a conserved principle in the skin. This study reveals an unanticipated plasticity of the adult skin epithelium when faced with mutational and non-mutational insult, and elucidates the dynamic cellular behaviours used for its return to a homeostatic state.
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