Jin Zhigang, Kirilly Daniel, Weng Changjiang, Kawase Eihachiro, Song Xiaoqing, Smith Sarah, Schwartz Joel, Xie Ting
Stowers Institute for Medical Research, 1000 East 50th Street, Kansas City, MO 64110, USA.
Cell Stem Cell. 2008 Jan 10;2(1):39-49. doi: 10.1016/j.stem.2007.10.021.
Rapid progress has recently been made regarding how the niche controls stem cell function, but little is yet known about how stem cells in the same niche interact with one another. In this study, we show that differentiation-defective Drosophila ovarian germline stem cells (GSCs) can outcompete normal ones for niche occupancy in a cadherin-dependent manner. The differentiation-defective bam or bgcn mutant GSCs invade the niche space of neighboring wild-type GSCs and gradually push them out of the niche by upregulating E-cadherin expression. Furthermore, the bam/bgcn-mediated GSC competition requires E-cadherin and normal GSC division, but not the self-renewal-promoting BMP niche signal, while different E-cadherin levels can sufficiently stimulate GSC competition. Therefore, we propose that GSCs have a competitive relationship for niche occupancy, which may serve as a quality control mechanism to ensure that accidentally differentiated stem cells are rapidly removed from the niche and replaced by functional ones.
最近在微环境如何控制干细胞功能方面取得了快速进展,但对于同一微环境中的干细胞如何相互作用却知之甚少。在本研究中,我们表明,分化缺陷的果蝇卵巢生殖系干细胞(GSC)能够以钙黏蛋白依赖的方式在微环境占据上胜过正常干细胞。分化缺陷的bam或bgcn突变型GSC侵入相邻野生型GSC的微环境空间,并通过上调E-钙黏蛋白的表达逐渐将它们挤出微环境。此外,bam/bgcn介导的GSC竞争需要E-钙黏蛋白和正常的GSC分裂,但不需要促进自我更新的BMP微环境信号,而不同的E-钙黏蛋白水平能够充分刺激GSC竞争。因此,我们提出GSC在微环境占据方面存在竞争关系,这可能作为一种质量控制机制,以确保意外分化的干细胞迅速从微环境中被清除并被功能性干细胞取代。