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）很快被激活，在新的毛发周期中分裂。已知HFSC的静止受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，并且比表皮中的其他细胞产生更多的乳酸。此外，乳酸的产生对于HFSC的激活似乎至关重要，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）缺失在遗传上促进HFSC中乳酸的产生，加速了它们的活化和毛发循环。最后，我们发现了通过刺激Myc水平或抑制Mpc1载体活性来增加乳酸盐产生的小分子，并且可以局部地诱导毛发周期。这些数据表明，HFSCs保持新陈代谢状态，使它们保持休眠状态，并迅速对适当的增殖刺激作出反应。