Fine scale analysis of gene expression in Drosophila melanogaster gonads reveals Programmed cell death 4 promotes the differentiation of female germline stem cells.
Fine scale analysis of gene expression in Drosophila melanogaster gonads reveals Programmed cell death 4 promotes the differentiation of female germline stem cells.
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DOI：
10.1186/1471-213x-12-4
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发表时间：
2012-01-17
影响因子：
--
通讯作者：
Andrews J
中科院分区：
文献类型：
--
作者：
Cash AC;Andrews J
生殖系干细胞（GSC）存在于果蝇雌性和雄性的性腺中，它们的适当维持以及它们的正确分化对于生育力和繁殖力是必不可少的。参与维持和分化的因子的分子特征是果蝇和干细胞研究的主要目标。虽然遗传研究已经确定了许多这些关键因素，但使用全基因组表达研究有可能大大增加我们对这些途径的了解。在这里，我们报告了一个全基因组表达的研究，使用激光切割显微切割分离生殖系干细胞，体细胞龛细胞，早期分化的生殖细胞从女性和男性性腺。对这些数据的分析，结合两个先前发表的全基因组GSC数据集，揭示了在特定细胞群中表达的候选基因集。这些基因之一，CG10990的果蝇直系同源的哺乳动物程序性细胞死亡4（Pdcd4）的调查，揭示了女性和男性生殖干细胞和早期分化的子细胞的表达。功能分析表明，虽然它不是卵子发生或精子发生所必需的，但它确实具有促进雌性GSC分化的功能。此外，在女性中，Pdcd4基因与关键分化基因大理石袋（bam）和干细胞更新因子eIF4A相互作用，这表明其在分化中的功能可能是一种途径。我们提出Pdcd4通过减轻eIF4A介导的Bam抑制来促进GSC子细胞的分化。
Germline stem cells (GSCs) are present in the gonads of Drosophila females and males, and their proper maintenance, as well as their correct differentiation, is essential for fertility and fecundity. The molecular characterization of factors involved in maintenance and differentiation is a major goal both in Drosophila and stem cell research. While genetic studies have identified many of these key factors, the use of genome-wide expression studies holds the potential to greatly increase our knowledge of these pathways. Here we report a genome-wide expression study that uses laser cutting microdissection to isolate germline stem cells, somatic niche cells, and early differentiating germ cells from female and male gonads. Analysis of this data, in association with two previously published genome-wide GSC data sets, revealed sets of candidate genes as putatively expressed in specific cell populations. Investigation of one of these genes, CG10990 the Drosophila ortholog of mammalian Programmed cell death 4 (Pdcd4), reveals expression in female and male germline stem cells and early differentiating daughter cells. Functional analysis demonstrates that while it is not essential for oogenesis or spermatogenesis, it does function to promote the differentiation of GSCs in females. Furthermore, in females, Pdcd4 genetically interacts with the key differentiation gene bag of marbles (bam) and the stem cell renewal factor eIF4A, suggesting a possible pathway for its function in differentiation. We propose that Pdcd4 promotes the differentiation of GSC daughter cells by relieving the eIF4A-mediated inhibition of Bam.