Stem cell competition orchestrates skin homeostasis and ageing

Nan Liu, Hiroyuki Matsumura (), Tomoki Kato, Shizuko Ichinose, Aki Takada, Takeshi Namiki, Kyosuke Asakawa, Hironobu Morinaga, Yasuaki Mohri, Adèle Arcangelis, Elisabeth Geroges-Labouesse, Daisuke Nanba and Emi K. Nishimura ()
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Nan Liu: Tokyo Medical and Dental University
Hiroyuki Matsumura: Tokyo Medical and Dental University
Tomoki Kato: Tokyo Medical and Dental University
Shizuko Ichinose: Tokyo Medical and Dental University
Aki Takada: Tokyo Medical and Dental University
Takeshi Namiki: Tokyo Medical and Dental University Graduate School and Faculty of Medicine
Kyosuke Asakawa: Tokyo Medical and Dental University
Hironobu Morinaga: Tokyo Medical and Dental University
Yasuaki Mohri: Tokyo Medical and Dental University
Adèle Arcangelis: Université de Strasbourg
Elisabeth Geroges-Labouesse: Université de Strasbourg
Daisuke Nanba: Tokyo Medical and Dental University
Emi K. Nishimura: Tokyo Medical and Dental University

Nature, 2019, vol. 568, issue 7752, 344-350

Abstract: Abstract 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.

Date: 2019
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DOI: 10.1038/s41586-019-1085-7

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