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

Nat Commun. 2017; 
WangXusheng,ChenHaiyan,TianRuiyun,ZhangYiling,DrutskayaMarina S,WangChengmei,GeJianfeng,FanZhimeng,KongDeqiang,WangXiaoxiao,CaiTing,ZhouYing,WangJingwen,WangJinmei,WangShan,QinZhihai,JiaHuanhuan,WuYue,LiuJia,NedospasovSergei A,TredgetEdward E,LinMei,LiuJianjun,JiangYuyang,WuYaoj
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Gene Synthesis The sequence of the murine Lgr5 promoter was obtained from Genecopoeia (USA). The Lgr5 promoter and mTNFR1 shRNA sequences were synthesized by GenScript (USA). Get A Quote

摘要

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 ... More

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