Genetic Control of Intestinal Stem Cells in the Drosophila Hindgut

果蝇后肠肠干细胞的遗传控制

• 批准号: 7895667
• 负责人: VOLKER HARTENSTEIN
• 金额: $ 31.51万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-07-17 至 2011-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7895667
• 关键词: Address; Adhesions; Adult; Anterior; Biological Models; Cell Cycle; Cell Proliferation; Cell Shape; Cell division; Cell physiology; Cells; Characteristics; Colon; Cyclin E; Development; Drosophila genus; E-Cadherin; Embryo; Epithelial; Equilibrium; Erinaceidae; Gene Chips; Genes; Genetic; Goals; Hindgut; Intestines; Journals; Knowledge; Ligands; Mediating; Midgut; Mind; Modeling; Names; Nature; Neoplasms; Organ; Output; Pathway interactions; Pattern; Phase; Phenotype; Population; Process; Proliferating; Property; Publishing; RNA Interference; Regenerative Medicine; Relative (related person); Research; Series; Signal Pathway; Signal Transduction; Source; Stem cells; System; Testing; Time; Transplantation; Undifferentiated; Villus; adult stem cell; arm; base; cell behavior; cell type; fly; follow-up; inhibitor/antagonist; insight; intestinal crypt; migration; notch protein; novel; pluripotency; programs; research study; self renewing cell; self-renewal; stem cell biology; stem cell niche; tumor

Most adult organs contain populations of slowly cycling, undifferentiated stem cells. Aside from maintaining their own numbers, stem cells produce progeny that differentiate into the various cell types of the organ they are located in. Adult stem cells are under intensive study with the goal in mind to use these cells in regenerative medicine. Furthermore, it has become clear that neoplastic growth typically takes off from stem cells or their proliferating progeny. One important population of adult stem cells are the epithelial stem cells of the intestine. We recently found in the Drosophila adult hindgut a stem cell system that shows a high degree of similarity to the mammalian intestinal stem cells, but at the same time is considerably simpler to analyze genetically and developmentally. Drosophila hindgut stem cells are confined to a short segment of the hindgut, the hindgut proliferation zone (HPZ). Within the HPZ, self renewal, proliferation and differentiation is controlled by local sources of four signaling pathways, the Wnt/Wingless, Hedgehog, Notch and Jak/Stat pathway. In the proposed project we will address some fundamental properties of the HPZ: what are the functional relationships between these pathways, and what aspect of stem cell behavior (cell cycle? adhesion? migration? pluripotency?) does each of them control? Furthermore, the rapid development and relative simplicity of the Drosophila intestinal tract gives us the opportunity to investigate when and how the HPZ with its special signaling properties during development. Finally, we want to screen for novel genes involved in adult stem cell proliferation. Our overall goal is to advance the knowledge of the fly HPZ system to a degree that makes it possible to formulate additional, specific and readily translatable research programs, using the fly hindgut stem cells as a model system.

大多数成人器官含有缓慢循环、未分化的干细胞群。 除了维持自己的数量外，干细胞还产生能够分化的后代 成体干细胞 深入研究的目的是在再生医学中使用这些细胞。 此外，很明显，肿瘤生长通常从干细胞开始 细胞或其增殖后代。成体干细胞的一个重要群体是 肠道上皮干细胞。我们最近在果蝇成体中发现 后肠是一种与哺乳动物高度相似的干细胞系统 肠干细胞，但同时基因分析要简单得多 并在发展上。果蝇后肠干细胞被限制在一小段 后肠，后肠增殖区（HPZ）。在 HPZ 内，自我更新， 增殖和分化由四种信号通路的局部来源控制， Wnt/Wingless、Hedgehog、Notch 和 Jak/Stat 途径。在拟议的项目中，我们 将讨论 HPZ 的一些基本属性：功能是什么 这些途径之间的关系，以及干细胞行为的哪些方面（细胞 循环？附着力？迁移？多能性？）它们各自控制吗？此外， 果蝇肠道的快速发展和相对简单给了我们 有机会研究 HPZ 何时以及如何以其特殊的信号特性 在开发过程中。最后，我们想要筛选参与成体茎的新基因 细胞增殖。我们的总体目标是将飞行 HPZ 系统的知识推进到 使得能够制定额外的、具体的和易于翻译的程度 研究计划，使用果蝇后肠干细胞作为模型系统。

项目成果

Origin and dynamic lineage characteristics of the developing Drosophila midgut stem cells.

• DOI: 10.1016/j.ydbio.2016.06.018
• 发表时间: 2016-08
• 期刊: Developmental biology
• 影响因子: 2.7
• 作者: S. Takashima;Patrick Aghajanian;A. Younossi‐Hartenstein;V. Hartenstein

Development of the Drosophila entero-endocrine lineage and its specification by the Notch signaling pathway.

果蝇肠道内分泌谱系的开发及其通过Notch信号通路的规范。

• DOI: 10.1016/j.ydbio.2011.01.039
• 发表时间: 2011-05-15
• 期刊: Developmental biology
• 影响因子: 2.7
• 作者: Takashima S;Adams KL;Ortiz PA;Ying CT;Moridzadeh R;Younossi-Hartenstein A;Hartenstein V
• 通讯作者: Hartenstein V

Genetic control of intestinal stem cell specification and development: a comparative view.

• DOI: 10.1007/s12015-012-9351-1
• 发表时间: 2012-06
• 期刊: STEM CELL REVIEWS AND REPORTS
• 影响因子: 4.8
• 作者: Takashima, Shigeo;Hartenstein, Volker
• 通讯作者: Hartenstein, Volker

Hematopoiesis and hematopoietic organs in arthropods.

节肢动物的造血和造血器官。

• DOI: 10.1007/s00427-012-0428-2
• 发表时间: 2013-03
• 期刊: Development genes and evolution
• 影响因子: 2.4
• 作者: Grigorian M;Hartenstein V
• 通讯作者: Hartenstein V

Hematopoiesis at the onset of metamorphosis: terminal differentiation and dissociation of the Drosophila lymph gland.

• DOI: 10.1007/s00427-011-0364-6
• 发表时间: 2011-08
• 期刊: Development genes and evolution
• 影响因子: 2.4
• 作者: Grigorian M;Mandal L;Hartenstein V
• 通讯作者: Hartenstein V