Glutamine protects mouse spermatogonial stem cells against NOX1-derived ROS for sustaining self-renewal division in vitro

被引：8

作者：

Miyazaki, Takehiro ^{[1
]}

Kanatsu-Shinohara, Mito ^{[1
]}

Ogonuki, Narumi ^{[2
]}

Matoba, Shogo ^{[2
]}

Ogura, Atsuo ^{[2
]}

Yabe-Nishimura, Chihiro ^{[3
]}

Zhang, Hongliang ^{[4
,5
]}

Pommier, Yves ^{[4
,5
]}

Trumpp, Andreas ^{[6
]}

Shinohara, Takashi ^{[1
]}

机构：

[1] Kyoto Univ, Grad Sch Med, Dept Mol Genet, Kyoto 6068501, Japan

[2] RIKEN, Bioresource Res Ctr, Tsukuba 3050074, Japan

[3] Kyoto Prefectural Univ Med, Dept Pharmacol, Kyoto 6068566, Japan

[4] NCI, Dev Therapeut Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA

[5] NCI, Lab Mol Pharmacol, Ctr Canc Res, NIH, Bethesda, MD 20892 USA

[6] Deutsch Krebsforsh Zentrum DKFZ, Div Stem Cells & Canc, D-69120 Heidelberg, Germany

来源：

DEVELOPMENT | 2023年 / 150卷 / 20期

关键词：

Glutamine; Nox1; Reactive oxygen species; Spermatogonial stem cells; MAINTENANCE; ASPARAGINE; METABOLISM; TRANSPLANTATION; EXPRESSION; TRANSPORT; CULTURE; TESTIS; MICE;

D O I：

10.1242/dev.201157

中图分类号：

Q [生物科学];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Reactive oxygen species (ROS) are generated from NADPH oxidases and mitochondria; they are generally harmful for stem cells. Spermatogonial stem cells (SSCs) are unique among tissue -stem cells because they undergo ROS-dependent self-renewal via NOX1 activation. However, the mechanism by which SSCs are protected from ROS remains unknown. Here, we demonstrate a crucial role for Gln in ROS protection using cultured SSCs derived from immature testes. Measurements of amino acids required for SSC cultures revealed the indispensable role of Gln in SSC survival. Gln induced Myc expression to drive SSC self-renewal in vitro, whereas Gln deprivation triggered Trp53-dependent apoptosis and impaired SSC activity. However, apoptosis was attenuated in cultured SSCs that lacked NOX1. In contrast, cultured SSCs lacking Top1mt mitochondria-specific topoisomerase exhibited poor mitochondrial ROS production and underwent apoptosis. Gln deprivation reduced glutathione production; supra-molar Asn supplementation allowed offspring production from SSCs cultured without Gln. Therefore, Gln ensures ROS-dependent SSC-self-renewal by providing protection against NOX1 and inducing Myc.

引用

页数：12

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