Department of Biological Sciences, Columbia University, New York, 10027, USA.
Nat Commun. 2012 Apr 3;3:769. doi: 10.1038/ncomms1765.
The mechanisms underlying adult stem cell behaviour are likely to be diverse and have not yet been investigated systematically. Here we conducted an unbiased genetic screen using Drosophila ovarian follicle stem cells to probe essential functions regulating self-renewal of epithelial stem cells. Surprisingly, we find that niche adhesion emerges as the most commonly affected essential stem cell property, and that proliferation is critical for stem cell maintenance. We also find that PI3K pathway activation enhances follicle stem cell function, whereas mitochondrial dysfunction and reactive oxygen species production lead to stem cell loss. Moreover, we find that most genes required specifically in the stem cell of the follicle stem cell lineage are widely expressed but are not required for the maintenance of ovarian germline stem cells. These findings highlight the fundamental characteristics of follicle stem cells as an important stem cell paradigm that contrasts with some other stem cell models, where repression of differentiation or relative quiescence is crucial.
成人干细胞行为的机制可能多种多样，尚未得到系统研究。在这里，我们使用果蝇卵巢滤泡干细胞进行了一项无偏遗传筛选，以探究调节上皮干细胞自我更新的基本功能。令人惊讶的是，我们发现，壁龛黏附成为受影响最普遍的基本干细胞特性，而增殖对于干细胞维持至关重要。我们还发现，PI3K 途径的激活增强了滤泡干细胞的功能，而线粒体功能障碍和活性氧的产生导致干细胞的丢失。此外，我们发现，滤泡干细胞谱系中的干细胞所特需的大多数基因广泛表达，但对于卵巢生殖干细胞的维持并非必需。这些发现突出了滤泡干细胞的基本特征，作为一个重要的干细胞范例，与其他一些干细胞模型形成对比，在这些模型中，分化的抑制或相对静止是至关重要的。
