Although normally dormant, hair follicle stem cells (HFSCs) quickly become activated to divide during a new hair cycle. The quiescence of HFSCs is known to be regulated by a number of intrinsic and extrinsic mechanisms. Here we provide several lines of evidence to demonstrate that HFSCs utilize glycolytic metabolism and produce significantly more lactate than other cells in the epidermis. Furthermore, lactate generation appears to be critical for the activation of HFSCs as deletion of lactate dehydrogenase (Ldha) prevented their activation. Conversely, genetically promoting lactate production in HFSCs through mitochondrial pyruvate carrier 1 (Mpc1) deletion accelerated their activation and the hair cycle. Finally, we identify small molecules that increase lactate production by stimulating Myc levels or inhibiting Mpc1 carrier activity and can topically induce the hair cycle. These data suggest that HFSCs maintain a metabolic state that allows them to remain dormant and yet quickly respond to appropriate proliferative stimuli.

中文翻译：

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乳酸脱氢酶活性驱动毛囊干细胞活化。


尽管通常处于休眠状态，但毛囊干细胞 (HFSC) 很快就会被激活，在新的毛发周期中进行分裂。已知 HFSC 的静止受到许多内在和外在机制的调节。在这里，我们提供了几条证据来证明 HFSC 利用糖酵解代谢并比表皮中的其他细胞产生更多的乳酸。此外，乳酸的产生似乎对于 HFSC 的激活至关重要，因为乳酸脱氢酶 (Ldha) 的缺失阻止了它们的激活。相反，通过线粒体丙酮酸载体 1 (Mpc1) 缺失从基因上促进 HFSC 的乳酸生成，加速了它们的激活和毛发周期。最后，我们确定了通过刺激 Myc 水平或抑制 Mpc1 载体活性来增加乳酸产生的小分子，并且可以局部诱导毛发周期。这些数据表明，HFSC 维持一种代谢状态，使它们能够保持休眠状态，同时对适当的增殖刺激做出快速反应。