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Macrophages induce AKT/β-catenin-dependent Lgr5+ stem cell activation and hair follicle regeneration through TNF

Author

Listed:
  • Xusheng Wang

    (School of Life Sciences, Tsinghua University
    The Shenzhen Key Laboratory of Health Sciences and Technology)

  • Haiyan Chen

    (The Shenzhen Key Laboratory of Health Sciences and Technology
    Tsinghua-Berkeley Shenzhen Institute (TBSI), Tsinghua University
    State Key Laboratory Breeding Base-Shenzhen Key Laboratory of Chemical Biology, Graduate School at Shenzhen, Tsinghua University)

  • Ruiyun Tian

    (The Shenzhen Key Laboratory of Health Sciences and Technology
    Shenzhen Peiyuan Biotechnology Company)

  • Yiling Zhang

    (The General Hospital of Chinese People's Liberation Army)

  • Marina S. Drutskaya

    (Engelhardt Institute of Molecular Biology, Russian Academy of Sciences)

  • Chengmei Wang

    (School of Life Sciences, Tsinghua University
    The Shenzhen Key Laboratory of Health Sciences and Technology)

  • Jianfeng Ge

    (School of Life Sciences, Tsinghua University
    The Shenzhen Key Laboratory of Health Sciences and Technology)

  • Zhimeng Fan

    (School of Life Sciences, Tsinghua University
    The Shenzhen Key Laboratory of Health Sciences and Technology)

  • Deqiang Kong

    (School of Life Sciences, Tsinghua University
    The Shenzhen Key Laboratory of Health Sciences and Technology)

  • Xiaoxiao Wang

    (School of Life Sciences, Tsinghua University
    The Shenzhen Key Laboratory of Health Sciences and Technology)

  • Ting Cai

    (School of Life Sciences, Tsinghua University
    The Shenzhen Key Laboratory of Health Sciences and Technology)

  • Ying Zhou

    (School of Life Sciences, Tsinghua University
    The Shenzhen Key Laboratory of Health Sciences and Technology)

  • Jingwen Wang

    (School of Life Sciences, Tsinghua University
    The Shenzhen Key Laboratory of Health Sciences and Technology)

  • Jinmei Wang

    (School of Life Sciences, Tsinghua University
    The Shenzhen Key Laboratory of Health Sciences and Technology)

  • Shan Wang

    (School of Life Sciences, Tsinghua University
    The Shenzhen Key Laboratory of Health Sciences and Technology)

  • Zhihai Qin

    (Institute of Biophysics, Chinese Academy of Sciences)

  • Huanhuan Jia

    (Guangdong Laboratory Animals Monitoring Institute, Guangdong Provincial Key Laboratory of Laboratory Animals)

  • Yue Wu

    (Guangdong Laboratory Animals Monitoring Institute, Guangdong Provincial Key Laboratory of Laboratory Animals)

  • Jia Liu

    (College of Life Sciences, Northeast Forestry University)

  • Sergei A. Nedospasov

    (Engelhardt Institute of Molecular Biology, Russian Academy of Sciences)

  • Edward E. Tredget

    (Wound Healing Research Group, University of Alberta)

  • Mei Lin

    (The Shenzhen Key Laboratory of Health Sciences and Technology)

  • Jianjun Liu

    (Medical Key Laboratory of Health Toxicology of Shenzhen, Shenzhen Center for Disease Control and Prevention)

  • Yuyang Jiang

    (State Key Laboratory Breeding Base-Shenzhen Key Laboratory of Chemical Biology, Graduate School at Shenzhen, Tsinghua University)

  • Yaojiong Wu

    (The Shenzhen Key Laboratory of Health Sciences and Technology
    Tsinghua-Berkeley Shenzhen Institute (TBSI), Tsinghua University)

Abstract

Skin stem cells can regenerate epidermal appendages; however, hair follicles (HF) lost as a result of injury are barely regenerated. Here we show that macrophages in wounds activate HF stem cells, leading to telogen–anagen transition (TAT) around the wound and de novo HF regeneration, mostly through TNF signalling. Both TNF knockout and overexpression attenuate HF neogenesis in wounds, suggesting dose-dependent induction of HF neogenesis by TNF, which is consistent with TNF-induced AKT signalling in epidermal stem cells in vitro. TNF-induced β-catenin accumulation is dependent on AKT but not Wnt signalling. Inhibition of PI3K/AKT blocks depilation-induced HF TAT. Notably, Pten loss in Lgr5+ HF stem cells results in HF TAT independent of injury and promotes HF neogenesis after wounding. Thus, our results suggest that macrophage-TNF-induced AKT/β-catenin signalling in Lgr5+ HF stem cells has a crucial role in promoting HF cycling and neogenesis after wounding.

Suggested Citation

  • Xusheng Wang & Haiyan Chen & Ruiyun Tian & Yiling Zhang & Marina S. Drutskaya & Chengmei Wang & Jianfeng Ge & Zhimeng Fan & Deqiang Kong & Xiaoxiao Wang & Ting Cai & Ying Zhou & Jingwen Wang & Jinmei , 2017. "Macrophages induce AKT/β-catenin-dependent Lgr5+ stem cell activation and hair follicle regeneration through TNF," Nature Communications, Nature, vol. 8(1), pages 1-14, April.
  • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_ncomms14091
    DOI: 10.1038/ncomms14091
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    Cited by:

    1. Yang Yang & Chenyu Chu & Li Liu & Chenbing Wang & Chen Hu & Shengan Rung & Yi Man & Yili Qu, 2023. "Tracing immune cells around biomaterials with spatial anchors during large-scale wound regeneration," Nature Communications, Nature, vol. 14(1), pages 1-15, December.

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