Foxp1 maintains hair follicle stem cell quiescence through regulation of Fgf18
Foxp1 maintains hair follicle stem cell quiescence through regulation of Fgf18
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DOI：
10.1242/dev.097477
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发表时间：
2013-09-15
期刊：
影响因子：
4.6
通讯作者：
Hoang Nguyen
中科院分区：
文献类型：
--
作者：
Leishman, Erin;Howard, Jeffrey M.;Hoang Nguyen
毛囊在整个成年生活中周期性地退化和再生，需要定期的干细胞激活来驱动这个周期。在毛发周期的静止期，毛囊干细胞保持静止状态，直到它们收到增殖信号。我们发现，叉头转录因子Foxp1对维持毛囊干细胞的静止至关重要。皮肤上皮细胞中Foxp1的缺失导致早熟干细胞激活，导致毛发周期的静止期急剧缩短。相反，角质形成细胞中Foxp1的过表达通过促进细胞周期停滞来阻止细胞增殖。最后，通过功能获得和功能丧失的研究，我们确定成纤维细胞生长因子18(Fgf18)是Foxp1的关键下游靶点。我们发现，外源性供应的FGF18可以防止Foxp1基因缺失小鼠的毛囊干细胞过早激活。由于Fgf18控制静止期的长度，并且是Foxp1的关键下游靶点，我们的数据强烈表明Foxp1通过控制Fgf18的表达来调节毛囊干细胞巢中的静止干细胞状态。
Hair follicles cyclically degenerate and regenerate throughout adult life and require regular stem cell activation to drive the cycle. In the resting phase of the hair cycle, hair follicle stem cells are maintained in a quiescent state until they receive signals to proliferate. We found that the forkhead transcription factor Foxp1 is crucial for maintaining the quiescence of hair follicle stem cells. Loss of Foxp1 in skin epithelial cells leads to precocious stem cell activation, resulting in drastic shortening of the quiescent phase of the hair cycle. Conversely, overexpression of Foxp1 in keratinocytes prevents cell proliferation by promoting cell cycle arrest. Finally, through both gain-and loss-of-function studies, we identify fibroblast growth factor 18 (Fgf18) as the key downstream target of Foxp1. We show that exogenously supplied FGF18 can prevent the hair follicle stem cells of Foxp1 null mice from being prematurely activated. As Fgf18 controls the length of the quiescent phase and is a key downstream target of Foxp1, our data strongly suggest that Foxp1 regulates the quiescent stem cell state in the hair follicle stem cell niche by controlling Fgf18 expression.