GDNF promotes hair formation and cutaneous wound healing by targeting bulge stem cells
GDNF promotes hair formation and cutaneous wound healing by targeting bulge stem cells
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DOI：
10.1038/s41536-020-0098-z
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发表时间：
2020-06-12
影响因子：
7.2
通讯作者：
Braun, Robert E.
中科院分区：
文献类型：
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作者：
Lisse, Thomas S.;Sharma, Manju;Braun, Robert E.
胶质细胞源性神经营养因子（GDNF）是一种研究充分的神经再生因子;然而，它支持毛发形成和皮肤伤口修复的程度尚不清楚。通过使用aGfra 1（GDNF家族受体α 1）基因敲入报告基因小鼠系，发现GDNF信号传导在毛发周期启动和脱毛后毛发形成的早期阶段发生在毛发隆突干细胞（BSC）内。GDNF的重组和转基因过表达均通过增强BSC的自我更新和BSC衍生的祖细胞在损伤部位转化为表皮细胞来促进BSC集落生长、毛发形成和创伤后皮肤修复。条件性消融BSCs中的Gfra 1会损害毛发周期的开始，而条件性消融BSCs中的GDNF家族成员信号转导子Ret会阻止毛发周期的开始和脱毛诱导的毛囊生长期发育。我们的研究结果表明，GDNF促进毛发形成和伤口修复，隆突干细胞是两者的关键介质。
Glial-cell-derived neurotrophic factor (GDNF) is a well-studied neuroregenerative factor; however, the degree to which it supports hair formation and skin wound repair is not known. By using aGfra1(GDNF family receptor alpha 1) knock-in reporter mouse line, GDNF signaling was found to occur within hair bulge stem cells (BSCs) during the initiation of the hair cycle and early stages of hair formation after depilation. Both recombinant and transgene overexpression of GDNF promoted BSC colony growth, hair formation, and skin repair after wounding through enhanced self-renewal of BSCs and commitment of BSC-derived progenitors into becoming epidermal cells at the injury site. Conditional ablation ofGfra1among BSCs impaired the onset of the hair cycle, while conditional ablation of the GDNF family member signal transducer,Ret, within BSCs prevented the onset of the hair cycle and depilation-induced anagen development of hair follicles. Our findings reveal that GDNF promotes hair formation and wound repair and that bulge stem cells are critical mediators of both.