Gene circuitry controlling a stem cell niche
Gene circuitry controlling a stem cell niche
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DOI：
10.1016/j.cub.2005.01.004
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发表时间：
2005-01-26
期刊：
影响因子：
9.2
通讯作者：
McKearin, D
中科院分区：
文献类型：
--
作者：
Chen, DH;McKearin, D
许多干细胞群体通过信号通路与基质细胞相互作用，了解这些相互作用是理解STEP细胞生物学的关键。在果蝇中，生殖系干细胞(GSC)的维持需要几个基因的调节，包括DPP、Piwi、Pumilio和bam[1-5]。GSCs还与帽细胞保持持续接触，这些细胞可能分泌控制这些基因表达所需的信号配体[6，7]。例如，DPP信号通过沉默GSC中分化因子bam的转录起作用[5]。尽管有许多研究，但尚不清楚Piwi和Pumilio在维持GSC功能方面扮演什么角色。Piwi主要是一种帽子细胞因子，而Pumilio主要是一种生殖细胞因子。通过分子和遗传学实验，我们证明piwi通过沉默bam来维持GSCs。相反，BAM沉默不需要Pumilio，这表明Pumilio通过一种不依赖于谷仓转录的机制维持GSC的命运。令人惊讶的是，我们发现，如果生殖细胞也缺乏Pumilio，它们可以在没有bam的情况下分化。这些发现提示了GSC维持的分子途径。DPP和Piwi依赖的信号在GSCs中协同作用以沉默bam，而Pumilio抑制促进分化的mRNAs的翻译。在成囊细胞中，积累的Barn蛋白对抗Pumilio，允许促进成囊细胞转录本的翻译。
Many stem cell populations interact with stromal cells via signaling pathways, and understanding these interactions is key for understanding stern cell biology. In Drosophila, germline stem cell (GSC) maintenance requires regulation of several genes, including dpp, piwi, pumilio, and bam [1-5]. GSCs also maintain continuous contact with cap cells that probably secrete the signaling ligands necessary for controlling expression of these genes [6, 7]. For example, dpp signaling acts by silencing transcription of the differentiation factor, bam, in GSCs [5]. Despite numerous studies, it is not clear what roles piwi, primarily a cap cell factor, and pumilio, a germ cell factor, play in maintaining GSC function. With molecular and genetic experiments, we show that piwi maintains GSCs by silencing bam. In contrast, pumilio is not required for bam, silencing, indicating that pumilio, maintains GSC fate by a mechanism not dependent on barn transcription. Surprisingly, we find that germ cells can differentiate without bam if they also lack pumilio. These findings suggest a molecular pathway for GSC maintenance. dpp- and piwi-dependent signaling act synergistically in GSCs to silence bam, whereas pumilio represses translation of differentiation-promoting mRNAs. In cystoblasts, accumulating Barn protein antagonizes pumilio, permitting the translation of cystoblast-promoting transcripts.