Suppr超能文献

YAP/Yorkie 在生殖系中调节生殖干细胞和生殖细胞龛细胞与年龄相关的衰退。

YAP/Yorkie in the germline modulates the age-related decline of germline stem cells and niche cells.

机构信息

University of Cambridge, Cambridge, United Kingdom.

School of Biological and Chemical Sciences, Queen Mary University of London, Mile End Road, London, United Kingdom.

出版信息

PLoS One. 2019 Apr 3;14(4):e0213327. doi: 10.1371/journal.pone.0213327. eCollection 2019.

Abstract

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.

摘要

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。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ede0/6447158/4779159f9bd2/pone.0213327.g001.jpg

文献检索

告别复杂PubMed语法,用中文像聊天一样搜索,搜遍4000万医学文献。AI智能推荐,让科研检索更轻松。

立即免费搜索

文件翻译

保留排版,准确专业,支持PDF/Word/PPT等文件格式,支持 12+语言互译。

免费翻译文档

深度研究

AI帮你快速写综述,25分钟生成高质量综述,智能提取关键信息,辅助科研写作。

立即免费体验