Lactate dehydrogenase activity drives hair follicle stem cell activation.
Lactate dehydrogenase activity drives hair follicle stem cell activation.
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DOI：
10.1038/ncb3575
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发表时间：
2017-09
影响因子：
21.3
通讯作者：
Lowry WE
中科院分区：
文献类型：
--
作者：
Flores A;Schell J;Krall AS;Jelinek D;Miranda M;Grigorian M;Braas D;White AC;Zhou JL;Graham NA;Graeber T;Seth P;Evseenko D;Coller HA;Rutter J;Christofk HR;Lowry WE
虽然通常处于休眠状态，但毛囊干细胞（HFSC）在新的毛发周期中迅速被激活分裂。HFSCs的静止期是由多种内在和外在机制调控的。在这里，我们提供了几条证据来证明HFSCs利用糖酵解代谢，并产生比表皮中其他细胞显著更多的乳酸。此外，乳酸产生似乎是HFSC活化的关键，因为乳酸脱氢酶（Ldha）的缺失阻止了它们的活化。相反，通过线粒体丙酮酸载体（Mpc1）缺失在HFSC中遗传促进乳酸产生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保持代谢状态，使它们保持休眠状态，但对适当的增殖刺激迅速作出反应。
While 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 (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 allow them to remain dormant and yet quickly respond to appropriate proliferative stimuli.
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影响因子：
23.9
作者：
Shin J;Berg DA;Zhu Y;Shin JY;Song J;Bonaguidi MA;Enikolopov G;Nauen DW;Christian KM;Ming GL;Song H
通讯作者：
Song H
影响因子：
46.9
作者：
Morris, RJ;Liu, YP;Cotsarelis, G
通讯作者：
Cotsarelis, G
影响因子：
3.6
作者：
Kellenberger, Antonia J.;Tauchi, Miyuki
通讯作者：
Tauchi, Miyuki
影响因子：
4.8
作者：
Patterson, Jessica N.;Cousteils, Katelyn;Joseph, Jamie W.
通讯作者：
Joseph, Jamie W.
DOI：
10.1038/sj.jidsp.5640241
发表时间：
1999-12-01
影响因子：
--
作者：
Paus, R;Müller-Röver, S;Botchkarev, VA
通讯作者：
Botchkarev, VA