Lgr6 marks epidermal stem cells with a nerve-dependent role in wound re-epithelialization.

Lgr6 marks epidermal stem cells with a nerve-dependent role in wound re-epithelialization.
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DOI:
10.1016/j.stem.2021.05.007
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发表时间:
2021-09-02
期刊:
影响因子:
23.9
通讯作者:
Rompolas P
Rompolas P
中科院分区:
医学1区
文献类型:
--
作者:
Huang S;Kuri P;Aubert Y;Brewster M;Li N;Farrelly O;Rice G;Bae H;Prouty S;Dentchev T;Luo W;Capell BC;Rompolas P

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干细胞支持成人器官的终生维持,但人们对其在损伤中的具体作用知之甚少。在这里,我们证明了Lgr6标记了一个区域受限的表皮干细胞群体,这些干细胞与神经相互作用,专门负责伤口的再上皮化。白喉毒素介导的Lgr6干细胞消融可延缓伤口愈合,而皮肤失神经表现出这种作用。使用活体成像来捕捉损伤后干细胞的动态,我们表明,随着神经的丧失,Lgr6干细胞在伤口上皮化的作用减弱。这导致了包括毛囊干细胞在内的其他干细胞群体的招募,这些干细胞部分补偿了伤口的闭合。单细胞谱系追踪和基因表达分析表明,Lgr6干细胞的命运随着其生态位的丧失而转向分化。我们的结论是,Lgr6表皮干细胞为损伤反应做好了准备,并与神经相互作用来调节自己的命运。Huang等人的研究成果。使用活体成像技术分析皮肤损伤期间离散干细胞群体的动态变化。这项研究表明,表皮中含有一群专门负责伤口愈合的干细胞,它们依赖神经来调节自己的命运。
Stem cells support the lifelong maintenance of adult organs but their specific roles during injury are poorly understood. Here, we demonstrate that Lgr6 marks a regionally restricted population of epidermal stem cells that interact with nerves and specialize in wound re-epithelialization. Diphtheria toxin-mediated ablation of Lgr6 stem cells delays wound healing, and skin denervation phenocopies this effect. Using intravital imaging to capture stem cell dynamics after injury, we show that wound re-epithelialization by Lgr6 stem cells is diminished following the loss of nerves. This induces the recruitment of other stem cell populations, including hair follicle stem cells, which partially compensate to mediate the wound closure. Single-cell lineage tracing and gene expression analysis reveal that the fate of Lgr6 stem cells is shifted towards differentiation following the loss of their niche. We conclude that Lgr6 epidermal stem cells are primed for injury response and interact with nerves to regulate their fate. Huang et al. use intravital imaging to analyze the dynamics of discrete populations of stem cells during skin injury. This study shows that the epidermis contains a population of stem cells that specialize in wound healing and depend on nerves for regulating their fate.
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