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Signalling by senescent melanocytes hyperactivates hair growth

Author

Listed:
  • Xiaojie Wang

    (University of California
    University of California
    University of California)

  • Raul Ramos

    (University of California
    University of California
    University of California)

  • Anne Q. Phan

    (University of California, San Diego)

  • Kosuke Yamaga

    (University of California
    University of California)

  • Jessica L. Flesher

    (University of California)

  • Shan Jiang

    (University of California
    University of California)

  • Ji Won Oh

    (Yonsei University College of Medicine
    Kyungpook National University and Hospital)

  • Suoqin Jin

    (University of California
    Wuhan University)

  • Sohail Jahid

    (University of California)

  • Chen-Hsiang Kuan

    (University of California
    University of California
    National Taiwan University Hospital
    National Taiwan University)

  • Truman Kt Nguyen

    (University of California
    University of California)

  • Heidi Y. Liang

    (University of California
    University of California)

  • Nitish Udupi Shettigar

    (University of California
    University of California
    Amplifica Holdings Group, Inc.)

  • Renzhi Hou

    (University of California
    University of California
    University of California)

  • Kevin H. Tran

    (University of California
    University of California)

  • Andrew Nguyen

    (University of California
    University of California)

  • Kimberly N. Vu

    (University of California
    University of California)

  • Jennie L. Phung

    (University of California
    University of California)

  • Jonard P. Ingal

    (University of California
    University of California)

  • Katelyn M. Levitt

    (University of California
    University of California)

  • Xiaoling Cao

    (University of California
    University of California)

  • Yingzi Liu

    (University of California
    University of California
    Xiangya Hospital, Central South University)

  • Zhili Deng

    (Xiangya Hospital, Central South University)

  • Nobuhiko Taguchi

    (Gifu University Graduate School of Medicine)

  • Vanessa M. Scarfone

    (University of California)

  • Guangfang Wang

    (University of California)

  • Kara Nicole Paolilli

    (University of California)

  • Xiaoyang Wang

    (University of California)

  • Christian F. Guerrero-Juarez

    (University of California
    University of California
    University of California
    University of California)

  • Ryan T. Davis

    (University of California)

  • Elyse Noelani Greenberg

    (University of California)

  • Rolando Ruiz-Vega

    (University of California)

  • Priya Vasudeva

    (University of California)

  • Rabi Murad

    (University of California
    University of California)

  • Lily Halida Putri Widyastuti

    (University of California)

  • Hye-Lim Lee

    (University of California
    University of California)

  • Kevin J. McElwee

    (University of Bradford)

  • Alain-Pierre Gadeau

    (University of Bordeaux, INSERM U1034, Adaptation cardiovasculaire à l’ischémie)

  • Devon A. Lawson

    (University of California)

  • Bogi Andersen

    (University of California
    University of California
    University of California
    University of California)

  • Ali Mortazavi

    (University of California
    University of California)

  • Zhengquan Yu

    (China Agricultural University)

  • Qing Nie

    (University of California
    University of California
    University of California
    University of California)

  • Takahiro Kunisada

    (Gifu University Graduate School of Medicine)

  • Michael Karin

    (University of California San Diego, School of Medicine)

  • Jan Tuckermann

    (University of Ulm, Helmholtzstrasse 8/1
    Leibniz Institute on Aging-Fritz Lipmann Institute, Beutenbergstrasse 11)

  • Jeffrey D. Esko

    (University of California, San Diego)

  • Anand K. Ganesan

    (University of California
    University of California)

  • Ji Li

    (Xiangya Hospital, Central South University
    Xiangya Hospital, Central South University)

  • Maksim V. Plikus

    (University of California
    University of California
    University of California
    University of California)

Abstract

Niche signals maintain stem cells in a prolonged quiescence or transiently activate them for proper regeneration1. Altering balanced niche signalling can lead to regenerative disorders. Melanocytic skin nevi in human often display excessive hair growth, suggesting hair stem cell hyperactivity. Here, using genetic mouse models of nevi2,3, we show that dermal clusters of senescent melanocytes drive epithelial hair stem cells to exit quiescence and change their transcriptome and composition, potently enhancing hair renewal. Nevus melanocytes activate a distinct secretome, enriched for signalling factors. Osteopontin, the leading nevus signalling factor, is both necessary and sufficient to induce hair growth. Injection of osteopontin or its genetic overexpression is sufficient to induce robust hair growth in mice, whereas germline and conditional deletions of either osteopontin or CD44, its cognate receptor on epithelial hair cells, rescue enhanced hair growth induced by dermal nevus melanocytes. Osteopontin is overexpressed in human hairy nevi, and it stimulates new growth of human hair follicles. Although broad accumulation of senescent cells, such as upon ageing or genotoxic stress, is detrimental for the regenerative capacity of tissue4, we show that signalling by senescent cell clusters can potently enhance the activity of adjacent intact stem cells and stimulate tissue renewal. This finding identifies senescent cells and their secretome as an attractive therapeutic target in regenerative disorders.

Suggested Citation

  • Xiaojie Wang & Raul Ramos & Anne Q. Phan & Kosuke Yamaga & Jessica L. Flesher & Shan Jiang & Ji Won Oh & Suoqin Jin & Sohail Jahid & Chen-Hsiang Kuan & Truman Kt Nguyen & Heidi Y. Liang & Nitish Udupi, 2023. "Signalling by senescent melanocytes hyperactivates hair growth," Nature, Nature, vol. 618(7966), pages 808-817, June.
    • Handle: RePEc:nat:nature:v:618:y:2023:i:7966:d:10.1038_s41586-023-06172-8
    DOI: 10.1038/s41586-023-06172-8
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    Citations

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    Cited by:

    1. Di-Yang Sun & Wen-Bin Wu & Jian-Jin Wu & Yu Shi & Jia-Jun Xu & Shen-Xi Ouyang & Chen Chi & Yi Shi & Qing-Xin Ji & Jin-Hao Miao & Jiang-Tao Fu & Jie Tong & Ping-Ping Zhang & Jia-Bao Zhang & Zhi-Yong Li, 2024. "Pro-ferroptotic signaling promotes arterial aging via vascular smooth muscle cell senescence," Nature Communications, Nature, vol. 15(1), pages 1-22, December.

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