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- Title
Macrophages induce AKT/β-catenin-dependent Lgr5<sup>+</sup> stem cell activation and hair follicle regeneration through TNF.
- Authors
Wang, Xusheng; Chen, Haiyan; Tian, Ruiyun; Zhang, Yiling; Drutskaya, Marina S.; Wang, Chengmei; Ge, Jianfeng; Fan, Zhimeng; Kong, Deqiang; Wang, Xiaoxiao; Cai, Ting; Zhou, Ying; Wang, Jingwen; Wang, Jinmei; Wang, Shan; Qin, Zhihai; Jia, Huanhuan; Wu, Yue; Liu, Jia; Nedospasov, Sergei A.
- 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.
- Publication
Nature Communications, 2017, Vol 8, Issue 3, p14091
- ISSN
2041-1723
- Publication type
Article
- DOI
10.1038/ncomms14091