期刊
STEM CELLS
卷 34, 期 7, 页码 1896-1908出版社
WILEY-BLACKWELL
DOI: 10.1002/stem.2363
关键词
Hair follicle stem cells; Morphogenesis; Ectodermal dysplasia; Shh
资金
- Swiss National Science Foundation [CRSI33_125459]
- Academy of Finland
- Sigrid Juselius Foundation
- Jane and Aatos Erkko Foundation
- Ella and Georg Ehrnrooth Foundation
- [RO1 DC013072]
- [RO3 DC007349]
- Swiss National Science Foundation (SNF) [CRSI33_125459] Funding Source: Swiss National Science Foundation (SNF)
The hair follicle is an ideal system to study stem cell specification and homeostasis due to its well characterized morphogenesis and stereotypic cycles of stem cell activation upon each hair cycle to produce a new hair shaft. The adult hair follicle stem cell niche consists of two distinct populations, the bulge and the more activation-prone secondary hair germ (HG). Hair follicle stem cells are set aside during early stages of morphogenesis. This process is known to depend on the Sox9 transcription factor, but otherwise the establishment of the hair follicle stem cell niche is poorly understood. Here, we show that that mutation of Foxi3, a Forkhead family transcription factor mutated in several hairless dog breeds, compromises stem cell specification. Further, loss of Foxi3 impedes hair follicle downgrowth and progression of the hair cycle. Genome-wide profiling revealed a number of downstream effectors of Foxi3 including transcription factors with a recognized function in hair follicle stem cells such as Lhx2, Runx1, and Nfatc1, suggesting that the Foxi3 mutant phenotype results from simultaneous downregulation of several stem cell signature genes. We show that Foxi3 displays a highly dynamic expression pattern during hair morphogenesis and cycling, and identify Foxi3 as a novel secondary HG marker. Absence of Foxi3 results in poor hair regeneration upon hair plucking, and a sparse fur phenotype in unperturbed mice that exacerbates with age, caused by impaired secondary HG activation leading to progressive depletion of stem cells. Thus, Foxi3 regulates multiple aspects of hair follicle development and homeostasis. Stem Cells2016;34:1896-1908
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据