Laboratory of Genetics, The Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA.
Curr Biol. 2010 Dec 7;20(23):2100-5. doi: 10.1016/j.cub.2010.10.038. Epub 2010 Nov 4.
When nutrient availability becomes limited, animals must actively adjust their metabolism to allocate limited resources and maintain tissue homeostasis. However, it is poorly understood how tissues maintained by adult stem cells respond to chronic changes in metabolism. To begin to address this question, we fed flies a diet lacking protein (protein starvation) and assayed both germline and intestinal stem cells. Our results revealed a decrease in stem cell proliferation and a reduction in stem cell number; however, a small pool of active stem cells remained. Upon refeeding, stem cell number increased dramatically, indicating that the remaining stem cells are competent to respond quickly to changes in nutritional status. Stem cell maintenance is critically dependent upon intrinsic and extrinsic factors that act to regulate stem cell behavior. Activation of the insulin/IGF signaling pathway in stem cells and adjacent support cells in the germline was sufficient to suppress stem cell loss during starvation. Therefore, our data indicate that stem cells can directly sense changes in the systemic environment to coordinate their behavior with the nutritional status of the animal, providing a paradigm for maintaining tissue homeostasis under metabolic stress.
当营养物质供应变得有限时，动物必须积极调整新陈代谢，以分配有限的资源并维持组织内稳态。然而，人们对成年干细胞维持的组织如何对代谢的慢性变化做出反应还知之甚少。为了开始解决这个问题，我们用缺乏蛋白质的饮食喂养果蝇（即蛋白质饥饿），并检测生殖细胞和肠道干细胞。我们的结果显示，干细胞增殖减少，干细胞数量减少；然而，一小部分活跃的干细胞仍然存在。重新喂食后，干细胞数量急剧增加，表明剩余的干细胞有能力对营养状况的变化迅速做出反应。干细胞的维持严重依赖于内在和外在因素，这些因素作用于调节干细胞的行为。生殖细胞中的干细胞和相邻支持细胞中胰岛素/IGF 信号通路的激活足以抑制饥饿期间干细胞的丢失。因此，我们的数据表明，干细胞可以直接感知全身环境的变化，使它们的行为与动物的营养状况相协调，为在代谢应激下维持组织内稳态提供了范例。
