Mechanisms Regulating Germline Stem Cells in Drosophila

描述(申请人提供)：成体干细胞可以在 每个分裂并产生终末分化的后代 成人组织中的动态平衡。理解成体干细胞的一个主要问题 一直是为了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，基质细胞已经被 假设为干细胞形成特殊的微环境或小生境。由于 在体内识别干细胞和周围干细胞的困难， 人们对干细胞壁龛的结构和功能知之甚少。 最近，我们证明了生殖系干细胞(GSC)的存在。 在果蝇卵巢中，干细胞及其周围细胞可以在那里 在体内进行了有效的研究。我们还发现了十足瘫痪(DPP)， 编码一种转化生长因子-β样生长因子，作为来自壁龛细胞的关键信号 规范GSC的自我更新和分裂。然而，仍然有许多 关于利基如何监管GSC的问题仍有待回答。 该项目的长期目标将是更好地了解 这些基因座如何调控干细胞，以及DPP和其他信号通路 参与干细胞和它们的壁龛之间的交流，以及 解释这些信号的干细胞中的内在因素。我们将重点关注 DPP途径如何调控GSC的自我更新和分化。我们的基因 筛查已经确定了影响GSC自我更新和 差异化。其中一些突变体的进一步分子特征 将揭示调控GSCs的重要分子机制。其作用机制 控制果蝇卵巢中的GSCs可能是 不同来源的干细胞对成年哺乳动物干细胞的认识 生物体具有相似的“茎”特性。此外，更好地理解 其中调控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 干细胞在临床上的应用以及用于治疗一些退行性疾病和 癌症。

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.