Myc/Mycn-mediated glycolysis enhances mouse spermatogonial stem cell self-renewal.
Myc/Mycn-mediated glycolysis enhances mouse spermatogonial stem cell self-renewal.
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DOI：
10.1101/gad.287045.116
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发表时间：
2016-12-01
影响因子：
10.5
通讯作者：
Shinohara T
中科院分区：
文献类型：
--
作者：
Kanatsu-Shinohara M;Tanaka T;Ogonuki N;Ogura A;Morimoto H;Cheng PF;Eisenman RN;Trumpp A;Shinohara T
Kanatsu-Shinohara等人研究了Myc调控精原干细胞（SSC）命运的机制。他们的研究结果表明，Myc介导的糖酵解是增加SSC自我更新分裂频率的重要因素。Myc在各种干细胞类型的自我更新分裂中起关键作用。在精原干细胞（SSC）中，Myc控制SSC命运决定，因为Myc过表达诱导增强的自我更新分裂，而Myc结合伴侣Max的耗尽导致减数分裂诱导。然而，Myc作用于SSC命运的机制尚不清楚。在这里，我们证明了在SSC自我更新中Myc/Mycn基因活性和糖酵解之间的关键联系。在SSC中，Myc/Mycn受Foxo 1调节，Foxo 1的缺乏会损害SSC的自我更新。Myc/Mycn缺陷的SSC不仅进行有限的自我更新分裂，而且显示出降低的糖酵解活性。虽然抑制糖酵解降低SSC活性，糖酵解的化学刺激或活性Akt 1或Pdpk 1（磷酸肌醇依赖性蛋白激酶1）的转染增强自我更新分裂，和长期的SSC培养物来自非许可的菌株，显示有限的自我更新分裂。这些结果表明，Myc介导的糖酵解是增加SSC自我更新分裂频率的重要因素。
Here, Kanatsu-Shinohara et al. investigated the mechanisms underlying Myc regulation of spermatogonial stem cell (SSC) fate. Their findings suggest that Myc-mediated glycolysis is an important factor that increases the frequency of SSC self-renewal division. Myc plays critical roles in the self-renewal division of various stem cell types. In spermatogonial stem cells (SSCs), Myc controls SSC fate decisions because Myc overexpression induces enhanced self-renewal division, while depletion of Max, a Myc-binding partner, leads to meiotic induction. However, the mechanism by which Myc acts on SSC fate is unclear. Here we demonstrate a critical link between Myc/Mycn gene activity and glycolysis in SSC self-renewal. In SSCs, Myc/Mycn are regulated by Foxo1, whose deficiency impairs SSC self-renewal. Myc/Mycn-deficient SSCs not only undergo limited self-renewal division but also display diminished glycolytic activity. While inhibition of glycolysis decreased SSC activity, chemical stimulation of glycolysis or transfection of active Akt1 or Pdpk1 (phosphoinositide-dependent protein kinase 1 ) augmented self-renewal division, and long-term SSC cultures were derived from a nonpermissive strain that showed limited self-renewal division. These results suggested that Myc-mediated glycolysis is an important factor that increases the frequency of SSC self-renewal division.
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