Hair follicle stem cells (HFSCs) in the bugle circularly generate outer root sheath (ORS) through linear proliferation within limited cycles during anagen phases. However, the mechanisms controlling the pace of HFSC proliferation remain unclear. Here we revealed that Foxp1, a transcriptional factor, was dynamically relocated from the nucleus to the cytoplasm of HFSCs in phase transitions from anagen to catagen, coupled with the rise of oxidative stress. Mass spectrum analyses revealed that the S468 phosphorylation of Foxp1 protein was responsive to oxidative stress and affected its nucleocytoplasmic translocation. Foxp1 deficiency in hair follicles led to compromised ROS accrual and increased HFSC proliferation. And more, NAC treatment profoundly elongated the anagen duration and HFSC proliferation in Foxp1-deficient background. Molecularly, Foxp1 augmented ROS levels through suppression of Trx1-mediated reductive function, thereafter imposing the cell cycle arrest by modulating the activity of p19/p53 pathway. Our findings identify a novel role for Foxp1 in controlling HFSC proliferation with cellular dynamic location in response to oxidative stress during hair cycling.

中文翻译：

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Foxp1调节毛囊干细胞中毛囊干细胞的增殖，以响应氧化应激。

号角中的毛囊干细胞（HFSC）在生长期的有限周期内通过线性增殖循环产生外根鞘（ORS）。但是，控制HFSC增殖速度的机制仍不清楚。在这里，我们揭示了Foxp1，一种转录因子，在从生长期到生长期的相变过程中，动态地从HFSC的细胞核转移到细胞质，并伴随着氧化应激的上升。质谱分析显示，Foxp1蛋白的S468磷酸化对氧化应激有反应，并影响其核质易位。毛囊中的Foxp1缺乏症导致ROS累积下降和HFSC增殖增加。而且，在缺乏Foxp1的背景下，NAC治疗极大地延长了生长期和HFSC的增殖。在分子上，Foxp1通过抑制Trx1介导的还原功能增加ROS水平，此后通过调节p19 / p53途径的活性强加细胞周期阻滞。我们的发现确定了Foxp1在毛发循环过程中响应氧化应激而控制细胞动态位置的HFSC增殖中的新型作用。