Lu Yanfen, Li Zhouhua
Plant Science and Technology College, Beijing University of Agriculture, Beijing 102206, China; Beijing Key Laboratory of New Technology in Agriculture Application, Beijing University of Agriculture, Beijing 102206, China.
School of Life Sciences, Capital Normal University, Beijing 100048, China.
Gene. 2015 Apr 10;560(1):89-95. doi: 10.1016/j.gene.2015.01.053. Epub 2015 Jan 28.
Adult tissue homeostasis is maintained by residential stem cells through the proper balance of stem cell self-renewal and differentiation. The adult midgut of Drosophila contains multipotent intestinal stem cells (ISCs), and Notch signaling plays critical roles in the proliferation and differentiation of these ISCs. However, how Notch signaling downstream targets regulate ISC proliferation and differentiation still remains unclear. Here we find that Notch signaling downstream targets E(spl)mbeta and E(spl)malpha are differentially expressed in ISCs and their progeny. Interestingly, we find that midgut homeostasis is not affected in E(spl)mbeta null mutant. No obvious defects are observed in the intestines ectopically expressing E(spl)mbeta or E(spl)malpha. Importantly, we find that the defects in ISC proliferation and differentiation observed in Notch mutant cannot be rescued by ectopic expression of E(spl)mbeta or E(spl)malpha. Together, these data indicate that the proliferation and differentiation of ISCs are not regulated by individual Notch downstream target, but by different downstream targets collectively.
成体组织稳态由驻留干细胞通过干细胞自我更新和分化的适当平衡来维持。果蝇的成体中肠含有多能肠干细胞（ISC），Notch信号通路在这些ISC的增殖和分化中起关键作用。然而，Notch信号通路的下游靶点如何调节ISC的增殖和分化仍不清楚。在这里，我们发现Notch信号通路的下游靶点E(spl)mbeta和E(spl)malpha在ISC及其子代中差异表达。有趣的是，我们发现在E(spl)mbeta基因敲除突变体中，中肠稳态不受影响。在异位表达E(spl)mbeta或E(spl)malpha的肠道中未观察到明显缺陷。重要的是，我们发现Notch突变体中观察到的ISC增殖和分化缺陷不能通过异位表达E(spl)mbeta或E(spl)malpha来挽救。总之，这些数据表明ISC的增殖和分化不是由单个Notch下游靶点调节的，而是由不同的下游靶点共同调节的。
