Department of Genetics and Development, Columbia University Medical Center, New York, NY 10032, USA.
Proc Natl Acad Sci U S A. 2011 Nov 15;108(46):18702-7. doi: 10.1073/pnas.1109348108. Epub 2011 Nov 2.
Drosophila adult midgut intestinal stem cells (ISCs) maintain tissue homeostasis by producing progeny that replace dying enterocytes and enteroendocrine cells. ISCs adjust their rates of proliferation in response to enterocyte turnover through a positive feedback loop initiated by secreted enterocyte-derived ligands. However, less is known about whether ISC proliferation is affected by growth of the progeny as they differentiate. Here we show that nutrient deprivation and reduced insulin signaling results in production of growth-delayed enterocytes and prolonged contact between ISCs and newly formed daughters. Premature disruption of cell contact between ISCs and their progeny leads to increased ISC proliferation and rescues proliferation defects in insulin receptor mutants and nutrient-deprived animals. These results suggest that ISCs can indirectly sense changes in nutrient and insulin levels through contact with their daughters and reveal a mechanism that could link physiological changes in tissue growth to stem cell proliferation.
果蝇成体肠道干细胞（ISCs）通过产生后代来维持组织稳态，这些后代可替代死亡的肠细胞和肠内分泌细胞。ISCs 通过由分泌的肠细胞衍生配体启动的正反馈回路，响应肠细胞周转率来调整其增殖速度。然而，对于 ISC 增殖是否会受到后代分化时生长的影响，人们知之甚少。在这里，我们发现营养剥夺和胰岛素信号转导降低会导致生长延迟的肠细胞产生，并延长 ISC 与新形成的子细胞之间的接触。过早破坏 ISC 与其后代之间的细胞接触会导致 ISC 增殖增加，并挽救胰岛素受体突变体和营养剥夺动物的增殖缺陷。这些结果表明，ISCs 可以通过与后代的接触间接感知营养和胰岛素水平的变化，并揭示了一种可能将组织生长的生理变化与干细胞增殖联系起来的机制。
