IDEAS home Printed from https://ideas.repec.org/a/nat/nature/v568y2019i7752d10.1038_s41586-019-1085-7.html
   My bibliography  Save this article

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
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41586-019-1085-7
    File Function: Abstract
    Download Restriction: Access to the full text of the articles in this series is restricted.
    File URL: https://libkey.io/10.1038/s41586-019-1085-7?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    As the access to this document is restricted, you may want to search for a different version of it.

    Citations

    Citations are extracted by the CitEc Project, subscribe to its RSS feed for this item.
    as


    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. 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.
    4. 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.
    5. 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.
    6. 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.
    7. 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.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:nature:v:568:y:2019:i:7752:d:10.1038_s41586-019-1085-7. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    We have no bibliographic references for this item. You can help adding them by using this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.