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Ectopic Dpp signaling promotes stem cell competition through EGFR signaling in the Drosophila testis

机译:异位Dpp信号通过果蝇睾丸中的EGFR信号促进干细胞竞争

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摘要

Stem cell competition could select the fittest stem cells and potentially control tumorigenesis. However, little is known about the underlying molecular mechanisms. Here, we find that ectopic Decapentaplegic (Dpp) signal activation by expressing a constitutively active form of Thickveins (TkvCA) in cyst stem cells (CySCs) leads to competition between CySCs and germline stem cells (GSCs) for niche occupancy and GSC loss. GSCs are displaced from the niche and undergo differentiation. Interestingly, we find that induction of TkvCA results in elevated expression of vein, which further activates Epidermal Growth Factor Receptor (EGFR) signaling in CySCs to promote their proliferation and compete GSCs out of the niche. Our findings elucidate the important role of Dpp signaling in regulating stem cell competition and tumorigenesis, which could be shed light on tumorigenesis and cancer treatment in mammals.
机译:干细胞竞争可以选择最适合的干细胞并潜在地控制肿瘤发生。然而,对潜在的分子机制知之甚少。在这里,我们发现,通过在囊性干细胞(CySCs)中表达一种构成活性形式的Thinveins(Tkv CA ),异位十足瘫痪(Dpp)信号激活导致CySC与种​​系干细胞(GSC)之间的竞争利基占有率和GSC损失。 GSC脱离了利基市场并经历了分化。有趣的是,我们发现诱导Tkv CA 导致静脉表达升高,从而进一步激活CySCs中的表皮生长因子受体(EGFR)信号,从而促进其增殖并竞争GSCs进入利基市场。我们的发现阐明了Dpp信号在调节干细胞竞争和肿瘤发生中的重要作用,这可能为哺乳动物的肿瘤发生和癌症治疗提供启示。

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