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Direct control of somatic stem cell proliferation factors by the Drosophila testis stem cell niche

机译:果蝇睾丸干细胞利基直接控制体细胞干细胞增殖因子

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Niches have traditionally been characterised as signalling microenvironments that allow stem cells to maintain their fate. This definition implicitly assumes that the various niche signals are integrated towards a binary fate decision between stemness and differentiation. However, observations in multiple systems have demonstrated that stem cell properties, such as proliferation and self-renewal, can be uncoupled at the level of niche signalling input, which is incompatible with this simplified view. We have studied the role of the transcriptional regulator Zfh1, a shared target of the Hedgehog and Jak/Stat niche signalling pathways, in the somatic stem cells of the Drosophila testis. We found that Zfh1 binds and downregulates salvador and kibra, two tumour suppressor genes of the Hippo/Wts/Yki pathway, thereby restricting Yki activation and proliferation to the Zfh1(+) stem cells. These observations provide an unbroken link from niche signal input to an individual aspect of stem cell behaviour that does not, at any step, involve a fate decision. We discuss the relevance of these findings for an overall concept of stemness and niche function.
机译:传统上,利基的特征在于一种允许干细胞保持其命运的信号传导微环境。该定义隐含地假设各种利基信号朝向茎干和分化之间的二进制命运决策集成。然而,在多种系统中的观察表明,干细胞性质,例如增殖和自我更新,可以在利基信令输入的水平下耦合,这与该简化视图不相容。我们已经研究了转录调节器ZFH1,刺猬和JAK / STAT信号传导途径的共同目标的作用,在果蝇睾丸的体细胞干细胞中。我们发现ZFH1结合和下调萨尔瓦多和kibra,两个肿瘤抑制基因的河马/ WTS / YKI途径,从而限制了YKI活化和增殖对ZFH1(+)干细胞。这些观察结果提供了来自利基信号输入的不间断的链路,该信号输入的单独的干细胞行为的各个方面,这些信号在任何步骤都不涉及命运决定。我们讨论了这些调查结果对茎干和利基功能的整体概念的相关性。

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