Stem cell competition orchestrates skin homeostasis and ageing
Autor: | Hiroyuki Matsumura, Adèle De Arcangelis, Emi K. Nishimura, Aki Takada, Tomoki Kato, Daisuke Nanba, Hironobu Morinaga, Kyosuke Asakawa, Shizuko Ichinose, Takeshi Namiki, Elisabeth Geroges-Labouesse, Nan Liu, Yasuaki Mohri |
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Rok vydání: | 2019 |
Předmět: |
0301 basic medicine
Multidisciplinary medicine.diagnostic_test Hemidesmosome Proteolysis Cell Biology In vitro Cell biology 03 medical and health sciences 030104 developmental biology 0302 clinical medicine medicine.anatomical_structure Ageing 030220 oncology & carcinogenesis medicine Stem cell Tissue homeostasis Homeostasis |
Zdroj: | Nature. 568:344-350 |
ISSN: | 1476-4687 0028-0836 |
Popis: | Stem cells underlie tissue homeostasis, but their dynamics during ageing—and the relevance of these dynamics to organ ageing—remain unknown. Here we report that the expression of the hemidesmosome component collagen XVII (COL17A1) by epidermal stem cells fluctuates physiologically through genomic/oxidative stress-induced proteolysis, and that the resulting differential expression of COL17A1 in individual stem cells generates a driving force for cell competition. In vivo clonal analysis in mice and in vitro 3D modelling show that clones that express high levels of COL17A1, which divide symmetrically, outcompete and eliminate adjacent stressed clones that express low levels of COL17A1, which divide asymmetrically. Stem cells with higher potential or quality are thus selected for homeostasis, but their eventual loss of COL17A1 limits their competition, thereby causing ageing. The resultant hemidesmosome fragility and stem cell delamination deplete adjacent melanocytes and fibroblasts to promote skin ageing. Conversely, the forced maintenance of COL17A1 rescues skin organ ageing, thereby indicating potential angles for anti-ageing therapeutic intervention. COL17A1-driven stem cell competition and symmetric cell divisions initially govern skin homeostasis, but the same mechanisms result in skin ageing later in life. |
Databáze: | OpenAIRE |
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