Functional differences between GDNF-dependent and FGF2-dependent mouse spermatogonial stem cell self-renewal.
Functional differences between GDNF-dependent and FGF2-dependent mouse spermatogonial stem cell self-renewal.
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DOI：
10.1016/j.stemcr.2015.01.010
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发表时间：
2015-03-10
影响因子：
5.9
通讯作者：
Shinohara, Takashi
中科院分区：
文献类型：
--
作者：
Takashima, Seiji;Kanatsu-Shinohara, Mito;Tanaka, Takashi;Morimoto, Hiroko;Inoue, Kimiko;Ogonuki, Narumi;Jijiwa, Mayumi;Takahashi, Masahide;Ogura, Atsuo;Shinohara, Takashi
精子发生需要精原干细胞（SSC）。早期研究表明，胶质细胞源性神经营养因子（GDNF）通过与 GFRA1/RET 受体结合，对于 SSC 的自我更新是不可或缺的。这些分子发生突变的小鼠表现出精子发生受损，这归因于 SSC 耗竭。在这里，我们展示了 SSC 进行不依赖 GDNF 的自我更新。当将 Ret 突变小鼠品系的睾丸片段移植到异源受体时，少量精原细胞形成集落。此外，补充成纤维细胞生长因子 2 (FGF2) 可以在没有 GDNF 的情况下实现体外 SSC 扩增。尽管 GDNF 介导的自我更新信号传导需要 AKT 和 MAP2K1/2，但后者在 FGF2 介导的自我更新中是可有可无的。 FGF2 耗尽的睾丸表现出 GDNF 水平升高，并且 SSC 富集，表明 FGF2 和 GDNF 水平之间的平衡影响 SSC 在体内的自我更新。我们的结果表明，SSC 至少表现出两种自我更新模式，并表明体内 SSC 调节的复杂性。 GDNF 对于精原干细胞 (SSC) 的自我更新是可有可无的 GFRA1 在大多数 SSC 中表达 生精小管中 FGF2 的体内消耗会丰富 SSC GDNF 的自我更新，而不是 FGF2，需要 MAP2K1/2 在本文中，Shinohara 及其同事表明，精原干细胞 （SSC）至少经历两种类型的自我更新。 GDNF被认为对于SSC的生存和自我更新是不可或缺的。然而，作者分析了 Ret 突变小鼠，发现 SSC 在没有 GDNF 的情况下也能进行自我更新。在没有 GDNF 的情况下，在体外重现了 SSC 的自我更新。
Spermatogonial stem cells (SSCs) are required for spermatogenesis. Earlier studies showed that glial cell line-derived neurotrophic factor (GDNF) was indispensable for SSC self-renewal by binding to the GFRA1/RET receptor. Mice with mutations in these molecules showed impaired spermatogenesis, which was attributed to SSC depletion. Here we show that SSCs undergo GDNF-independent self-renewal. A small number of spermatogonia formed colonies when testis fragments from a Ret mutant mouse strain were transplanted into heterologous recipients. Moreover, fibroblast growth factor 2 (FGF2) supplementation enabled in vitro SSC expansion without GDNF. Although GDNF-mediated self-renewal signaling required both AKT and MAP2K1/2, the latter was dispensable in FGF2-mediated self-renewal. FGF2-depleted testes exhibited increased levels of GDNF and were enriched for SSCs, suggesting that the balance between FGF2 and GDNF levels influences SSC self-renewal in vivo. Our results show that SSCs exhibit at least two modes of self-renewal and suggest complexity of SSC regulation in vivo. GDNF is dispensable for spermatogonial stem cell (SSC) self-renewal GFRA1 is expressed in most SSCs In vivo depletion of FGF2 in the seminiferous tubules enriches SSCs Self-renewal by GDNF, but not FGF2, requires MAP2K1/2 In this article, Shinohara and colleagues show that spermatogonial stem cells (SSCs) undergo at least two types of self-renewal. GDNF is thought to be indispensable for SSC survival and self-renewal. However, the authors analyzed Ret mutant mice and found that SSCs undergo self-renewal without GDNF. SSC self-renewal was recapitulated in vitro without GDNF.
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