The Beatson Institute for Cancer Research; Glasgow, UK.
Cell Cycle. 2013 Sep 15;12(18):2973-7. doi: 10.4161/cc.26031. Epub 2013 Aug 12.
Adult stem cells are responsible for maintaining the balance between cell proliferation and differentiation within self-renewing tissues. The molecular and cellular mechanisms mediating such balance are poorly understood. The production of reactive oxygen species (ROS) has emerged as an important mediator of stem cell homeostasis in various systems. Our recent work demonstrates that Rac1-dependent ROS production mediates intestinal stem cell (ISC) proliferation in mouse models of colorectal cancer (CRC). Here, we use the adult Drosophila midgut and the mouse small intestine to directly address the role of Rac1 in ISC proliferation and tissue regeneration in response to damage. Our results demonstrate that Rac1 is necessary and sufficient to drive ISC proliferation and regeneration in an ROS-dependent manner. Our data point to an evolutionarily conserved role of Rac1 in intestinal homeostasis and highlight the value of combining work in the mammalian and Drosophila intestine as paradigms to study stem cell biology.
成体干细胞负责维持自我更新组织中细胞增殖和分化之间的平衡。介导这种平衡的分子和细胞机制还了解甚少。活性氧（ROS）的产生已成为各种系统中干细胞动态平衡的重要介质。我们最近的工作表明，Rac1 依赖性 ROS 产生介导了结直肠癌（CRC）小鼠模型中肠干细胞（ISC）的增殖。在这里，我们使用成年果蝇中肠和小鼠小肠直接研究 Rac1 在 ISC 增殖和组织再生对损伤的反应中的作用。我们的结果表明，Rac1 以 ROS 依赖性方式驱动 ISC 增殖和再生是必需和充分的。我们的数据表明 Rac1 在肠道动态平衡中具有保守的作用，并强调了将哺乳动物和果蝇肠道的工作相结合作为研究干细胞生物学范例的价值。
