Mechanisms Regulating Germline Stem Cells in Drosophila

果蝇生殖干细胞的调节机制

• 批准号: 6620370
• 负责人: TING XIE
• 金额: $ 22.26万
• 依托单位: STOWERS INSTITUTE FOR MEDICAL RESEARCH
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-01-01 至 2006-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6620370
• 关键词: Drosophilidae; biological signal transduction; cell cell interaction; cell differentiation; cell growth regulation; gene expression; genetic regulation; genetic screening; genotype; in situ hybridization; intermolecular interaction; ovary; polymerase chain reaction; stem cells; transforming growth factors

DESCRIPTION (provided by applicant): Adult stem cells can renew themselves at each division and generate terminally differentiated progeny that maintain homeostasis in adult tissues. A major issue in understanding adult stem cells has been to distinguish whether regulation is primarily controlled by internal or external mechanisms. In mammalian systems, stromal cells have been hypothesized to form special microenvironments or niches for stem cells. Due to the difficulty in identifying stem cells and surrounding stem cells in vivo, there is little known about the structure and function of stem cell niches. Recently, we have demonstrated the existence of germline stem cell (GSC) niches in the Drosophila ovary, where stem cells and their surrounding cells can be effectively studied in vivo. We have also identified decapentaplegic (dpp), encoding a TGF-beta-like growth factor, as a key signal from the niche cells regulating GSC self-renewal and division. However, there are still many questions that remain to be answered regarding how the niche regulates GSCs. The long-term goal of this project will be to gain a greater understanding of how the niches regulate stem cells, and of dpp and other signaling pathways involved in the communication between stem cells and their niches, and of intrinsic factors in stem cells that interpret these signals. We will focus on how the dpp pathway regulates GSC self-renewal and differentiation. Our genetic screens have identified mutants that affect GSC self-renewal and differentiation. Further molecular characterization of some of these mutants will reveal important molecular mechanisms regulating GSCs. The mechanisms controlling GSCs in the Drosophila ovary are likely to be fundamental to the understanding of adult mammalian stem cells since stem cells from diverse organisms share similar "stem" properties. In addition, a better understanding of the mechanisms regulating stem cells is of considerable clinical relevance, since the pathways and genes involved will provide valuable information for using stem cells clinically and for treating some degenerative diseases and cancer.

描述（由申请人提供）：成体干细胞可以自我更新 每次分裂并产生终末分化的后代，维持 成人组织的稳态。了解成体干细胞的一个主要问题 区分监管是否主要由内部控制 或外部机制。在哺乳动物系统中，基质细胞已被 假设为干细胞形成特殊的微环境或生态位。由于 体内识别干细胞和周围干细胞的困难， 人们对干细胞巢的结构和功能知之甚少。 最近，我们证明了生殖干细胞（GSC）生态位的存在 在果蝇卵巢中，干细胞及其周围的细胞可以 有效地进行了体内研究。我们还发现了十瘫痪 (dpp)， 编码 TGF-β 样生长因子，作为来自微环境细胞的关键信号 调节 GSC 的自我更新和分裂。然而，仍然有很多 关于利基市场如何监管 GSC 的问题仍有待回答。 该项目的长期目标是加深对 生态位如何调节干细胞、dpp 和其他信号通路 参与干细胞及其生态位之间的通讯，以及 干细胞中解释这些信号的内在因素。我们将重点关注 dpp 通路如何调节 GSC 自我更新和分化。我们的基因 筛选已鉴定出影响 GSC 自我更新的突变体 差异化。其中一些突变体的进一步分子表征 将揭示调节 GSC 的重要分子机制。机制 控制果蝇卵巢中的 GSC 可能是 对成年哺乳动物干细胞的了解，因为干细胞来自不同的 生物体具有相似的“茎”特性。另外，更好的理解 调节干细胞的机制具有相当大的临床意义， 因为所涉及的途径和基因将为 临床上使用干细胞来治疗一些退行性疾病和 癌症。