Mnt对果蝇神经干细胞行为和命运决定调控机制的研究
结题报告
批准号:
31970675
项目类别:
面上项目
资助金额:
58.0 万元
负责人:
王苏
依托单位:
学科分类:
细胞命运及重编程
结题年份:
2023
批准年份:
2019
项目状态:
已结题
项目参与者:
王苏
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中文摘要
干细胞的行为与命运决定对多种组织器官的正常发育至关重要,其调控机制的紊乱可能会导致严重的发育疾病。申请人前期工作表明,果蝇神经干细胞中的转录调控因子Mnt被敲降后,会导致干细胞及其后代细胞数量的显著减少。有趣的是,这一表型与Myc敲降的结果类似。我们认为,Mnt在神经干细胞中会发挥异于其传统拮抗Myc的功能,但是具体作用机制尚不清楚。本项目将重点研究果蝇神经发育时期,Mnt对神经干细胞行为和命运决定的调控机制。拟实现目标:一、检测Mnt及相关因子在神经干细胞及其子代细胞中的动态表达水平;二、鉴定Mnt对神经干细胞行为和命运决定的调控功能;三、阐明Mnt调控干细胞命运的具体分子机制;四、鉴定Mnt上游通路,探索通过调节Mnt水平,抑制神经干细胞瘤样过度增殖和过早缺失的可能性。本项目旨在加深对神经干细胞行为和命运决定调控机制的认识,并为未来临床上治疗相关神经发育疾病提供实验证据和理论基础。
英文摘要
The regulation of stem cell behavior and fate decision plays an important role in the development of various tissues and organs. The disorder of regulation may lead to serious developmental diseases. Our preliminary research showed that Mnt knockdown in drosophila neural stem cells, neuroblasts, lead to a significant reduction in the number of stem cells and their lineages. Interestingly, this is similar to the phenotype of Myc knockdown. We believe that Mnt in neuroblasts will play a different role from its traditional function as a Myc antagonist, but its specific regulatory mechanism is still unclear. This project aims to study the regulation mechanism of Mnt on cell behavior and fate decision of Drosophila neuroblasts during neurogenesis. We propose to fulfill the following objectives: 1. To detect the expression level of Mnt and related factors in neuroblasts as well as their progeny cells; 2. To identify the regulatory function of Mnt on cell behavior and fate decision of neuroblasts; 3. To elucidate the molecular mechanism of regulation function of Mnt; 4. To identify the upstream pathway of Mnt and to explore the possibility of inhibition to neural stem cell tumor-like overproliferation and premature loss through Mnt. This project aims to deepen our understanding of the regulatory mechanism of neural stem cell behavior and fate decision. It will also provide experimental evidence and theoretical basis for the future clinical treatment of related neurodevelopmental diseases.
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DOI:10.1016/j.isci.2023.108545
发表时间:2024-01-19
期刊:ISCIENCE
影响因子:5.8
作者:Zhang, Huanhuan;Rui, Menglong;Ma, Zhixin;Gong, Sifan;Zhang, Shuliu;Zhou, Qingxia;Gan, Congfeng;Gong, Wenting;Wang, Su
通讯作者:Wang, Su
微环境中缝隙连接对果蝇神经干细胞自我更新与分化的调控机制
  • 批准号:
    31771510
  • 项目类别:
    面上项目
  • 资助金额:
    25.0万元
  • 批准年份:
    2017
  • 负责人:
    王苏
  • 依托单位:
国内基金
海外基金