University of Cambridge, Cambridge, United Kingdom.
School of Biological and Chemical Sciences, Queen Mary University of London, Mile End Road, London, United Kingdom.
PLoS One. 2019 Apr 3;14(4):e0213327. doi: 10.1371/journal.pone.0213327. eCollection 2019.
The properties and behaviour of stem cells rely heavily on signaling from the local microenvironment. At the apical end of Drosophila testis, self-renewal and differentiation of germline stem cells (GSCs) are tightly controlled by distinct somatic cells that comprise a specialised stem cell niche known as the hub. The hub maintains GSC homeostasis through adhesion and cell signaling. The Salvador/Warts/Hippo (SWH) pathway, which suppresses the transcriptional co-activator YAP/Yki via a kinase cascade, is a known regulator of stem cell proliferation and differentiation. Here, we show that increasing YAP/Yki expression in the germline, as well as reducing Warts levels, blocks the decrease of GSC numbers observed in aging flies, with only a small increase on their proliferation. An increased expression of YAP/Yki in the germline or a reduction in Warts levels also stymies an age-related reduction in hub cell number, suggesting a bilateral relationship between GSCs and the hub. Conversely, RNAi-based knockdown of YAP/Yki in the germline leads to a significant drop in hub cell number, further suggesting the existence of such a SC-to-niche relationship. All together, our data implicate the SWH pathway in Drosophila GSC maintenance and raise questions about its role in stem cell homeostasis in aging organisms.
干细胞的特性和行为在很大程度上依赖于局部微环境的信号。在果蝇睾丸的顶端,生殖干细胞(GSCs)的自我更新和分化受到由特化的干细胞龛(称为“枢纽”)中的特定体细胞的严格控制。枢纽通过黏附和细胞信号来维持 GSC 的稳态。Salvador/Warts/Hippo (SWH) 途径通过激酶级联抑制转录共激活因子 YAP/Yki,是干细胞增殖和分化的已知调节剂。在这里,我们表明,增加生殖系中的 YAP/Yki 表达,以及降低 Warts 水平,可以阻止在衰老果蝇中观察到的 GSC 数量减少,而仅略微增加其增殖。生殖系中 YAP/Yki 的表达增加或 Warts 水平的降低也会抑制与年龄相关的枢纽细胞数量减少,这表明 GSCs 和枢纽之间存在双向关系。相反,基于 RNAi 的生殖系中 YAP/Yki 的敲低会导致枢纽细胞数量的显著下降,这进一步表明存在这种 SC 到龛的关系。总之,我们的数据表明 SWH 途径参与了果蝇 GSC 的维持,并提出了关于其在衰老生物体中干细胞稳态中的作用的问题。