Lisse Thomas S, Sharma Manju, Vishlaghi Neda, Pullagura Sri Ramulu, Braun Robert E
The Jackson Laboratory, 600 Main Street, Bar Harbor, ME 04609 USA.
Department of Biology, The University of Miami, 1301 Memorial Drive, Cox Science Building, Coral Gables, FL 33124 USA.
NPJ Regen Med. 2020 Jun 12;5:13. doi: 10.1038/s41536-020-0098-z. eCollection 2020.
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 a (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 of among BSCs impaired the onset of the hair cycle, while conditional ablation of the GDNF family member signal transducer, , 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.
胶质细胞源性神经营养因子（GDNF）是一种经过充分研究的神经再生因子；然而，其对毛发形成和皮肤伤口修复的支持程度尚不清楚。通过使用一种（GDNF家族受体α1）敲入报告基因小鼠品系，发现GDNF信号在毛发周期开始时以及脱毛后毛发形成的早期阶段在毛囊隆突干细胞（BSCs）内发生。GDNF的重组表达和转基因过表达均通过增强BSCs的自我更新以及使BSC衍生的祖细胞在损伤部位分化为表皮细胞，促进了BSC集落生长、毛发形成和伤口愈合。在BSCs中条件性敲除会损害毛发周期的开始，而在BSCs中条件性敲除GDNF家族成员信号转导子则会阻止毛发周期的开始以及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，并且隆突干细胞是这两者的关键介质。
