Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai, Japan.
Genes Cells. 2020 May;25(5):343-349. doi: 10.1111/gtc.12762. Epub 2020 Mar 10.
Reactive oxygen species (ROS) often injure intestinal epithelia that cause loss of damaged cells, which is mainly repaired by proliferation of intestinal stem cells (ISCs). To maintain the homeostatic state, coordination of sensing of the ROS injury and the subsequent epithelial cell loss with the replenishment by cell renewal is crucial. However, little is known about how gut epithelial cells initiate regenerative responses against ROS to maintain the tissue integrity. Here, we carried out a genome-wide screen, by which we identify immunoglobulin superfamily beaten path Ib (beat-Ib) as an essential gene for provoking ISC proliferation against ROS in Drosophila intestine. Interestingly, the beat-Ib function is required in differentiated enterocytes, the main targeted cells by ROS in the intestinal tract, but is dispensable in the stem cells. Moreover, beat-Ib is not involved in enterocyte apoptosis at ROS injury. These findings indicate the essential role of beat-Ib in Drosophila midgut enterocytes for initiating the non-cell-autonomous induction of ISC division in response to environmental ROS stresses.
活性氧 (ROS) 通常会损伤肠道上皮细胞，导致受损细胞的损失，而这主要是由肠道干细胞 (ISCs) 的增殖来修复的。为了维持内稳态，ROS 损伤的感应以及随后的上皮细胞损失与细胞更新的补充之间的协调至关重要。然而，人们对肠道上皮细胞如何启动针对 ROS 的再生反应以维持组织完整性知之甚少。在这里，我们进行了全基因组筛选，发现免疫球蛋白超家族 beaten path Ib (beat-Ib) 是果蝇肠道中引发 ISC 增殖以对抗 ROS 的必需基因。有趣的是，beat-Ib 的功能在分化的肠细胞中是必需的，肠细胞是肠道中 ROS 的主要靶向细胞，但在干细胞中是可有可无的。此外，beat-Ib 不参与 ROS 损伤时的肠细胞凋亡。这些发现表明 beat-Ib 在果蝇中肠上皮细胞中对于启动非细胞自主诱导 ISC 分裂以响应环境 ROS 应激至关重要。
