The miRNA pathway intrinsically controls self-renewal of Drosophila germline stem cells
The miRNA pathway intrinsically controls self-renewal of Drosophila germline stem cells
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DOI：
10.1016/j.cub.2007.01.060
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发表时间：
2007-03-20
期刊：
影响因子：
9.2
通讯作者：
Liu, Qinghua
中科院分区：
文献类型：
--
作者：
Park, Joseph K.;Liu, Xiang;Liu, Qinghua
干细胞独特地自我更新并通过分化成不同的细胞类型来替代老化或受损的细胞来维持组织稳态[1]。在果蝇卵子发生过程中，生殖干细胞（GSC）的自我更新需要内在信号机制和来自邻近小生境细胞的外在信号[2]。新出现的证据表明，microRNA（miRNA）介导的翻译调控也可能控制果蝇GSC自我更新[3，4]。然而，目前还不清楚miRNA通路是否在干细胞或小生境细胞中起作用以维持GSC。在果蝇中，Dicer-1（Dcr-1）和双链RNA结合蛋白Loquacious（Loqs）催化miRNA生物合成[3-5]。在这里，我们产生loqs敲除（loqs（KO））苍蝇的末端同源重组，并表明loqs是胚胎生存能力和卵巢GSC的维护所必需的。发育和miRNA加工缺陷都通过Loqs-PB的转基因表达而不是Loqs-PA的转基因表达来挽救。此外，嵌合生殖系分析表明，Loqs是GSC维持所固有的。一致地，GSC通过Loqs-PB的种系表达而不是体细胞表达在loqs突变卵巢中恢复。总之，这些结果表明，Loqs-PB，而不是Loqs-PA，是必要的和足够的果蝇发育和miRNA途径。我们的研究有力地表明，miRNAs在果蝇雌性GSC自我更新中发挥内在而非外在的作用。
Stem cells uniquely self-renew and maintain tissue homoeostasis by differentiating into different cell types to replace aged or damaged cells [1]. During oogenesis of Drosophila melanogaster, self-renewal of germline stem cells (GSCs) requires both intrinsic signaling mechanisms and extrinsic signals from neighboring niche cells [2]. Emerging evidence suggests that microRNA (miRNA)-mediated translational regulation may also control Drosophila GSC self-renewal [3,4]. It is unclear, however, whether the miRNA pathway functions within stem cells or niche cells to maintain GSCs. In Drosophila, Dicer-1 (Dcr-1) and the double-stranded RNA binding protein Loquacious (Loqs) catalyze miRNA biogenesis [3-5]. Here, we generate loqs knockout (loqs(KO)) flies by ends-out homologous recombination and show that loqs is essential for embryonic viability and ovarian GSC maintenance. Both developmental and miRNA processing defects are rescued by transgenic expression of Loqs-PB, but not Loqs-PA. Furthermore, mosaic germline analysis indicates that Loqs is required intrinsically for GSC maintenance. Consistently, GSCs are restored in loqs mutant ovaries by germline expression, but not somatic expression, of Loqs-PB. Together, these results demonstrate that Loqs-PB, but not Loqs-PA, is necessary and sufficent for Drosophila development and the miRNA pathway. Our study strongly suggests that miRNAs play an intrinsic, but not extrinsic, role in Drosophila female GSC self-renewal.