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Stem cell competition orchestrates skin homeostasis and ageing

Author

Listed:
  • 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)

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.

Suggested Citation

  • Nan Liu & Hiroyuki Matsumura & Tomoki Kato & Shizuko Ichinose & Aki Takada & Takeshi Namiki & Kyosuke Asakawa & Hironobu Morinaga & Yasuaki Mohri & Adèle Arcangelis & Elisabeth Geroges-Labouesse & Dai, 2019. "Stem cell competition orchestrates skin homeostasis and ageing," Nature, Nature, vol. 568(7752), pages 344-350, April.
    • Handle: RePEc:nat:nature:v:568:y:2019:i:7752:d:10.1038_s41586-019-1085-7
    DOI: 10.1038/s41586-019-1085-7
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    Cited by:

    1. Elle Koren & Alona Feldman & Marianna Yusupova & Avihay Kadosh & Egor Sedov & Roi Ankawa & Yahav Yosefzon & Waseem Nasser & Stefanie Gerstberger & Liam B. Kimel & Noa Priselac & Samara Brown & Sam Sha, 2022. "Thy1 marks a distinct population of slow-cycling stem cells in the mouse epidermis," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    2. Fang Ye & Guodong Zhang & Weigao E. & Haide Chen & Chengxuan Yu & Lei Yang & Yuting Fu & Jiaqi Li & Sulei Fu & Zhongyi Sun & Lijiang Fei & Qile Guo & Jingjing Wang & Yanyu Xiao & Xinru Wang & Peijing , 2022. "Construction of the axolotl cell landscape using combinatorial hybridization sequencing at single-cell resolution," Nature Communications, Nature, vol. 13(1), pages 1-18, December.
    3. Hisato Nagano & Naoaki Mizuno & Hideyuki Sato & Eiji Mizutani & Ayaka Yanagida & Mayuko Kano & Mariko Kasai & Hiromi Yamamoto & Motoo Watanabe & Fabian Suchy & Hideki Masaki & Hiromitsu Nakauchi, 2024. "Skin graft with dermis and appendages generated in vivo by cell competition," Nature Communications, Nature, vol. 15(1), pages 1-12, December.
    4. Nanase Igarashi & Kenichi Miyata & Tze Mun Loo & Masatomo Chiba & Aki Hanyu & Mika Nishio & Hiroko Kawasaki & Hao Zheng & Shinya Toyokuni & Shunsuke Kon & Keiji Moriyama & Yasuyuki Fujita & Akiko Taka, 2022. "Hepatocyte growth factor derived from senescent cells attenuates cell competition-induced apical elimination of oncogenic cells," Nature Communications, Nature, vol. 13(1), pages 1-11, December.
    5. Hirofumi Nagao & Ashok Kumar Jayavelu & Weikang Cai & Hui Pan & Jonathan M. Dreyfuss & Thiago M. Batista & Bruna B. Brandão & Matthias Mann & C. Ronald Kahn, 2023. "Unique ligand and kinase-independent roles of the insulin receptor in regulation of cell cycle, senescence and apoptosis," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    6. Sunmin Park & Suna Kang & Woo Jae Lee, 2021. "Menopause, Ultraviolet Exposure, and Low Water Intake Potentially Interact with the Genetic Variants Related to Collagen Metabolism Involved in Skin Wrinkle Risk in Middle-Aged Women," IJERPH, MDPI, vol. 18(4), pages 1-12, February.
    7. Marianna Yusupova & Roi Ankawa & Yahav Yosefzon & David Meiri & Ido Bachelet & Yaron Fuchs, 2023. "Apoptotic dysregulation mediates stem cell competition and tissue regeneration," Nature Communications, Nature, vol. 14(1), pages 1-20, December.
    8. Alina C. Teuscher & Cyril Statzer & Anita Goyala & Seraina A. Domenig & Ingmar Schoen & Max Hess & Alexander M. Hofer & Andrea Fossati & Viola Vogel & Orcun Goksel & Ruedi Aebersold & Collin Y. Ewald, 2024. "Longevity interventions modulate mechanotransduction and extracellular matrix homeostasis in C. elegans," Nature Communications, Nature, vol. 15(1), pages 1-20, December.

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