线粒体呼吸链复合体I对果蝇肠道干细胞增殖分化的调控作用及内在机制

干细胞增殖与分化之间的平衡一旦打破则易形成肿瘤干细胞（Cancer stem cells, CSCs）, CSCs对肿瘤的起源、复发和转移具有决定性作用。线粒体呼吸链复合物I（mitochondrial complex I, MCI）在电子传递及氧化磷酸化过程中起关键作用，越来越多的研究表明MCI也调控干细胞的增殖分化。果蝇肠道是目前研究干细胞增殖分化调控的一个理想器官模型，之前实验中我们建立了活体病理模型来模拟肿瘤发生和转移不同阶段，抑制MCI表达后肠道组织恢复稳态，提示MCI下调使干细胞增殖分化失衡得到改善。本项目中，我们拟进一步观测MCI对不同状态下干细胞增殖分化的调控作用，并通过果蝇遗传学操作、分子生物学、细胞生物学和转录组测序等实验方法在ROS、AMPK信号通路和糖代谢途径等方面揭示MCI调控干细胞增殖分化的可能内在机制，为靶向MCI的分阶段针对性治疗肿瘤提供理论基础。

Tissue homeostasis is regulated by tightly controlled division and differentiation of multipotent somatic stem cells that give rise to different cell types of a given tissue. CSCs play a decisive role in the origin, recurrence and metastasis of tumors. Mitochondrial respiratory complex I (MCI) plays a key role in electron transfer and oxidative phosphorylation. More and more studies have shown that MCI also regulates the proliferation and differentiation of stem cells. Here, we used Drosophila midgut intestinal stem cell (ISCs) as an in vivo model system to simulate the tumor occurrence and metastasis of different stages. Downregulation of MCI expression in pathological groups makes the balance of self-renewal and differentiation to restore. We proposed a further observation of regulation function of MCI on differentiation and proliferation of stem cells under different states. The possible internal regulatory mechanisms of MCI in proliferation and differentiation of stem cells would be revealed in terms of ROS, AMPK signaling pathway and glucose metabolism pathway through Drosophila genetic manipulation, molecular biology, cell biology and transcriptome sequencing, etc., which would provide a theoretical basis for the MCI targeted treatment of tumors.