Somatic stem cells in the Drosophila ovary

果蝇卵巢中的成体干细胞

• 批准号: 8839780
• 负责人: DANIEL D KALDERON
• 金额: $ 35.2万
• 依托单位: COLUMBIA UNIV NEW YORK MORNINGSIDE
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-30 至 2018-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8839780
• 关键词: 1-Phosphatidylinositol 3-Kinase; Adhesions; Anterior; B-Lymphocytes; Cancerous; Cell Adhesion; Cell Count; Cell Lineage; Cell Maintenance; Cell Proliferation; Cell model; Cells; Complex; Daughter; Development; Drosophila genus; Environment; Epithelial; Erinaceidae; Future; Gap Junctions; Genetic; Genetic Models; Genotype; Health; Image; Imagery; Individual; Integrins; Intestines; Knowledge; Link; Literature; Location; Malignant Neoplasms; Measures; Mediating; Medicine; Methods; Modeling; Molecular; Mutation; Organism; Outcome; Ovary; Paneth Cells; Pathway interactions; Physiological; Physiology; Play; Population; Positioning Attribute; Property; Recording of previous events; Regulation; Reserve Stem Cell; Role; Signal Pathway; Signal Transduction; Stem Cell Factor; Stem cells; Testing; Time; adult stem cell; base; cell behavior; cell motility; cell type; combat; daughter cell; design; genetic approach; human stem cells; improved; insight; interest; life history; migration; novel strategies; regenerative therapy; response; self-renewal; smoothened signaling pathway; stem cell population; transcriptome sequencing

DESCRIPTION (provided by applicant): Stem cells must self-renew and produce daughters that differentiate. Consequently, stem cells are generally supported only in restricted locations that regulate proliferation and direct appropriate daughter cell fates. Somatic follicle stem cells (FSCs) in the Drosophila ovary provide an exceptional opportunity to study how the niche environment regulates stem cell behavior. Key advantages of the FSC model include advanced knowledge of regulation by multiple signaling pathways, an important role of competition between stem cells, and regulation of both niche adhesion and proliferation as key parameters of stem cell maintenance. Both the general principles discovered about FSC dynamics and regulation, as well as the impact of specific signaling pathways will provide important insights fo understanding the normal regulation of mammalian epithelial stem cells and how pre-cancerous mutations that arise in stem cells are selected and amplified. This proposal aims first to employ multiple genetic methods for lineage tracing together with a marker of cellular proliferative histories and live imaging to extend recent studies that promise a substantial advance in our understanding of FSC numbers, arrangement and dynamics. The anticipated outcomes would reveal remarkable similarities to the dynamics of mammalian intestinal stem cells. They would also explain why FSC maintenance and competition depends critically on proliferation and would show three potential fates of FSC daughters correlated with the direction of cell migration. The proliferative contribution of relevant signaling pathways will be defined and mechanistic connections will be investigated. Specific hypotheses that Wnt and JAK-STAT signaling pathways guide FSC derivative migration and fates, and that integrins may mediate some effects of JAK-STAT signaling will be tested. Finally, transcriptional responses to signaling pathways in FSCs will be measured as part of an overall objective to understand both the general principles and the molecular steps by which the niche environment regulates FSC behaviors that fit their specific physiological purpose.

描述（由申请人提供）：干细胞必须自我更新并产生能够分化的子细胞。因此，干细胞通常仅在调节增殖和指导适当的子细胞命运的有限位置得到支持。体细胞卵泡干细胞 果蝇卵巢中的 FSC（FSC）为研究生态位环境如何调节干细胞行为提供了绝佳的机会。 FSC 模型的主要优势包括对多种信号通路调节的深入了解、干细胞之间竞争的重要作用以及作为干细胞维持的关键参数的生态位粘附和增殖的调节。关于 FSC 动力学和调节的一般原理，以及特定信号通路的影响，将为理解哺乳动物上皮干细胞的正常调节以及干细胞中出现的癌前突变如何被选择和放大提供重要的见解。 该提案的目的首先是采用多种遗传方法进行谱系追踪，并结合细胞增殖历史标记和实时成像来扩展最近的研究，这些研究有望在我们对 FSC 数量、排列和动态的理解方面取得实质性进展。预期结果将揭示与哺乳动物肠道干细胞动力学的显着相似之处。他们还将解释为什么 FSC 的维持和竞争关键取决于增殖，并显示 FSC 子代的三种潜在命运与细胞迁移方向相关。将定义相关信号通路的增殖贡献并研究机制连接。 Wnt 和 JAK-STAT 信号通路指导 FSC 衍生物迁移和命运，以及整合素可能介导 JAK-STAT 信号传导的一些作用的具体假设将得到测试。最后，将测量 FSC 对信号通路的转录反应，作为总体目标的一部分，以了解利基环境调节 FSC 行为以适应其特定生理目的的一般原理和分子步骤。