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The Drosophila midgut: A model of human intestinal stem cells and their progeny.

果蝇中肠：人类肠道干细胞及其后代的模型。

基本信息

批准号：
8397662
负责人：
Benjamin Ohlstein
金额：
$ 26.49万
依托单位：
COLUMBIA UNIVERSITY HEALTH SCIENCES
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-04-23 至 2013-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8397662
关键词：
Address Adult Animal Model Animals Architecture Behavior Biological Models Cell Count Cells Clone Cells Data Daughter Development Diabetes Mellitus Diet Digestive System Disorders Drosophila genus Drosophila melanogaster Employee Strikes Enterocytes Enteroendocrine Cell Environmental Risk Factor Epithelial Cells Erinaceidae Event Excision Health Homeostasis Hormones Human Infection Injury Intestinal Cancer Intestines Label Ligands Maintenance Malabsorption Syndromes Midgut Modeling Molecular Multipotent Stem Cells Nature Nutrient Pathogenesis Production Property Regulation Reporter Research Role Secretory Cell Signal Pathway Signal Transduction Starvation Stem cells Stromal Cells System Tissues Ursidae Family Vertebrates adult stem cell base delta protein gene function insight insulin signaling mutant notch protein programs response stem cell division stem cell niche

项目摘要

DESCRIPTION (provided by applicant): Recently, we have identified stem cells (ISCs) in the Drosophila adult midgut that replenish the intestine throughout the entire lifetime of the animal. Drosophila ISCs, like vertebrate ISCs, are multipotent, producing both enterocytes and enteroendocrine cells. Furthermore, as in vertebrates, Drosophila ISCs utilize Notch signaling to produce an appropriate fraction of enteroendocrine cells and enterocytes. The relatively small cell number and simplicity of the Drosophila midgut allows one to identify ISCs morphologically under various conditions. Moreover, it is possible to remove gene function in marked clones of these cells in order to decipher the nature and directionality of signaling events. Based on our findings we will take advantage of the anatomically simpler but functionally relevant Drosophila system to address the following three specific aims. 1. Determine the cellular and molecular mechanisms that maintain Drosophila ISCs in a stem cell niche. 2. Identify the effects of nutrients, insulin signaling, and developmental signaling pathways like wingless and hedgehog on stem cell division, stability and differentiation. 3. Study how intercellular signals and environmental factors control the differentiation of enteroendocrine cells. HEALTH RELEVANCE. We have previously shown the maintenance and function of the adult Drosophila midgut bears many striking similarities to that seen in the human intestine. Therefore the results of our research should provide valuable insights into the pathogenesis of human digestive disorders such as intestinal cancers, malabsorption syndromes, and diabetes.

描述（由申请人提供）：最近，我们在果蝇成年中肠中发现了干细胞（ISCs），它们在动物的整个生命周期中补充肠道。果蝇ISCs与脊椎动物ISCs一样，具有多能性，既能产生肠细胞，也能产生肠内分泌细胞。此外，与脊椎动物一样，果蝇ISCs利用Notch信号产生适当比例的肠内分泌细胞和肠细胞。果蝇中肠相对较小的细胞数量和简单性允许人们在不同条件下从形态学上识别ISCs。此外，有可能去除这些细胞的标记克隆中的基因功能，以破译信号事件的性质和方向性。基于我们的发现，我们将利用解剖学上更简单但功能相关的果蝇系统来解决以下三个具体目标。1. 确定维持果蝇ISCs在干细胞生态位中的细胞和分子机制。2. 确定营养物质、胰岛素信号和发育信号通路如无翼和刺猬对干细胞分裂、稳定性和分化的影响。3. 研究细胞间信号和环境因素对肠内分泌细胞分化的调控作用。健康的相关性。我们之前已经证明，成年果蝇中肠的维持和功能与人类肠道有许多惊人的相似之处。因此，我们的研究结果将为人类消化系统疾病（如肠癌、吸收不良综合征和糖尿病）的发病机制提供有价值的见解。