ROS-Generating Oxidase Nox3 Regulates the Self-Renewal of Mouse Spermatogonial Stem Cells
ROS-Generating Oxidase Nox3 Regulates the Self-Renewal of Mouse Spermatogonial Stem Cells
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DOI：
10.1095/biolreprod.114.127647
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发表时间：
2015-06-01
影响因子：
3.6
通讯作者：
Shinohara, Takashi
中科院分区：
文献类型：
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作者：
Morimoto, Hiroko;Kanatsu-Shinohara, Mito;Shinohara, Takashi
精原干细胞（SSC）代表了具有自我更新潜力的独特生殖细胞群。尽管活性氧 (ROS) 被认为对生殖细胞有毒，但我们最近表明，SSC 自我更新需要中等水平的 ROS，并且 Nox1 参与 ROS 的生成。在这项研究中，我们表明自我更新因子治疗诱导 Nox3 触发 SSC 自我更新。 Nox3 在 FGF2 和 GDNF 刺激下在培养的精原细胞中短暂表达，而 Nox1 主要在增殖的稳定期表达。短发夹 RNA 抑制 Nox3 可减少细胞因子诱导的 ROS 生成，并限制培养精原细胞的增殖。尽管Nox3过表达没有显示出明显的效果，但Nox3的消耗减少了培养的精原细胞和新鲜分离的睾丸细胞中SSC的数量。我们的结果表明SSCs的自我更新是通过不同Nox基因的顺序激活来调节的，并强调了SSCs自我更新分裂中ROS调节的复杂性。
Spermatogonial stem cells (SSCs) represent a unique population of germ cells with self-renewal potential. Although reactive oxygen species (ROS) are considered toxic to germ cells, we recently showed that moderate levels of ROS are required for SSC self-renewal and that Nox1 is involved in ROS generation. In this study, we showed that self-renewal factor treatment induces Nox3 to trigger SSC self-renewal. Nox3 was transiently expressed in cultured spermatogonia by FGF2 and GDNF stimulation, whereas Nox1 was expressed predominantly during the stable phase of proliferation. Nox3 inhibition by short hairpin RNA reduced cytokine-induced ROS generation and limited the proliferation of cultured spermatogonia. Although Nox3 overexpression revealed no apparent effect, depletion of Nox3 decreased the number of SSCs in both cultured spermatogonia and freshly isolated testis cells. Our results suggest that self-renewal of SSCs is regulated by sequential activation of different Nox genes, and underscore the complexity of ROS regulation in the self-renewal division of SSCs.