Department of Biological Sciences, Columbia University, New York, NY 10027, USA.
Dev Cell. 2012 Oct 16;23(4):836-48. doi: 10.1016/j.devcel.2012.09.010.
We have used Drosophila ovarian follicle stem cells (FSCs) to study how stem cells are regulated by external signals and draw three main conclusions. First, the spatial definition of supportive niche positions for FSCs depends on gradients of Hh and JAK-STAT pathway ligands, which emanate from opposite, distant sites. FSC position may be further refined by a preference for low-level Wnt signaling. Second, hyperactivity of supportive signaling pathways can compensate for the absence of the otherwise essential adhesion molecule, DE-cadherin, suggesting a close regulatory connection between niche adhesion and niche signals. Third, FSC behavior is determined largely by summing the inputs of multiple signaling pathways of unequal potencies. Altogether, our findings indicate that a stem cell niche need not be defined by short-range signals and invariant cell contacts; rather, for FSCs, the intersection of gradients of long-range niche signals regulates the longevity, position, number, and competitive behavior of stem cells.
我们利用果蝇卵巢滤泡干细胞（FSCs）来研究干细胞如何受到外部信号的调控，并得出了三个主要结论。首先，FSCs 的支持性龛位的空间定义取决于 Hh 和 JAK-STAT 信号通路配体的梯度，这些梯度从相反的远距离位置发出。FSC 位置可能通过对低水平 Wnt 信号的偏好进一步细化。其次，支持性信号通路的过度活跃可以补偿缺失的必要黏附分子 DE-cadherin，表明龛位黏附和龛位信号之间存在紧密的调控联系。第三，FSC 的行为主要取决于多个信号通路的输入，这些信号通路的强度不同。总的来说，我们的发现表明，干细胞龛不一定由短程信号和不变的细胞接触来定义；相反，对于 FSCs 来说，长程龛位信号梯度的交点调节了干细胞的寿命、位置、数量和竞争行为。
