Srlp is crucial for the self-renewal and differentiation of germline stem cells via RpL6 signals in Drosophila testes
Srlp is crucial for the self-renewal and differentiation of germline stem cells via RpL6 signals in Drosophila testes
复制标题
在果蝇睾丸中，Srlp 通过 RpL6 信号对生殖干细胞的自我更新和分化至关重要
DOI：
10.1038/s41419-019-1527-z
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发表时间：
2019-04-01
影响因子：
9
通讯作者：
Fang, Jie
中科院分区：
文献类型：
--
作者：
Yu, Jun;Yan, Yidan;Fang, Jie
生殖系干细胞（GSCs）的自我更新和分化受到干细胞生态位和多种途径的严格调控。在之前的研究中，我们在果蝇睾丸中筛选了新的GSC调控基因Srlp。然而，Srlp和干细胞生态位之间的潜在机制联系在很大程度上仍未确定。本文通过对果蝇模型的遗传操作，系统分析了Srlp在体内和体外的功能和作用机制。在果蝇中，Srlp是调节睾丸中GSCs自我更新和分化的重要基因。在体外实验中，我们发现Srlp能够控制S2细胞的增殖能力和细胞死亡，这与在果蝇睾丸中观察到的表型一致。此外，液相色谱-串联质谱分析（LC-MS/MS）结果显示RpL6与Srlp结合。Srlp还通过RpL6信号调控剪接体和核糖体亚基的表达，控制剪接体和核糖体的功能。总的来说，我们的发现揭示了干细胞生态位的遗传原因和分子机制。本研究为阐明男性不育的发病机制和睾丸生殖细胞瘤的形成提供了新的思路。
Self-renewal and differentiation in germline stem cells (GSCs) are tightly regulated by the stem cell niche and via multiple approaches. In our previous study, we screened the novel GSC regulatory gene Srlp in Drosophila testes. However, the underlying mechanistic links between Srlp and the stem cell niche remain largely undetermined. Here, using genetic manipulation of the Drosophila model, we systematically analyze the function and mechanism of Srlp in vivo and in vitro. In Drosophila, Srlp is an essential gene that regulates the self-renewal and differentiation of GSCs in the testis. In the in vitro assay, Srlp is found to control the proliferation ability and cell death in S2 cells, which is consistent with the phenotype observed in Drosophila testis. Furthermore, results of the liquid chromatography-tandem mass spectrometry (LC-MS/MS) reveal that RpL6 binds to Srlp. Srlp also regulates the expression of spliceosome and ribosome subunits and controls spliceosome and ribosome function via RpL6 signals. Collectively, our findings uncover the genetic causes and molecular mechanisms underlying the stem cell niche. This study provides new insights for elucidating the pathogenic mechanism of male sterility and the formation of testicular germ cell tumor.