Huang Xudong, Shi Lai, Cao Jun, He Fangfei, Li Renling, Zhang Yan, Miao Shuang, Jin Longjin, Qu Jia, Li Zhouhua, Lin Xinhua
School of Optometry and Ophthalmology and Eye Hospital, Wenzhou Medical University, Wenzhou 325000, China.
State Key Laboratory of Biomembrane and Membrane Biotechnology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China.
J Genet Genomics. 2014 Aug 20;41(8):429-38. doi: 10.1016/j.jgg.2014.05.007. Epub 2014 Jun 19.
The proliferation and differentiation of adult stem cells must be tightly controlled in order to maintain resident tissue homeostasis. Dysfunction of stem cells is implicated in many human diseases, including cancer. However, the regulation of stem cell proliferation and differentiation is not fully understood. Here we show that the sterile-like 20 kinase, Tao, controls tissue homeostasis by regulating the Hippo pathway in the Drosophila adult midgut. Depletion of Tao in the progenitors leads to rapid intestinal stem cell (ISC) proliferation and midgut homeostasis loss. Meanwhile, we find that the Janus kinase (JAK)/signal transducer and activator of transcription (STAT) signaling activity and cytokine production are significantly increased, resulting in stimulated ISC proliferation. Furthermore, expression of the Hippo pathway downstream targets, Diap1 and bantam, is dramatically increased in Tao knockdown intestines. Consistently, we show that the Yorkie (Yki) acts downstream of Tao to regulate ISC proliferation. Together, our results provide insights into our understanding of the mechanisms of stem cell proliferation and tissue homeostasis control.
为维持组织内稳态，成体干细胞的增殖与分化必须受到严格调控。干细胞功能失调与包括癌症在内的多种人类疾病相关。然而，干细胞增殖与分化的调控机制尚未完全明晰。在此，我们表明类无菌20激酶Tao通过调控果蝇成虫中肠的Hippo信号通路来控制组织内稳态。祖细胞中Tao的缺失会导致肠道干细胞（ISC）迅速增殖以及中肠内稳态丧失。同时，我们发现Janus激酶（JAK）/信号转导及转录激活因子（STAT）信号活性和细胞因子产生显著增加，从而刺激ISC增殖。此外，在Tao敲低的肠道中，Hippo信号通路下游靶点Diap1和bantam的表达显著增加。同样，我们发现Yorkie（Yki）在Tao下游发挥作用以调控ISC增殖。总之，我们的研究结果为深入理解干细胞增殖及组织内稳态控制机制提供了见解。
