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.

大多数成年器官都包含缓慢循环，未分化的干细胞的种群。 除了保持自己的数量外，干细胞还会产生分化的后代 进入它们所在的器官的各种细胞类型。成年干细胞在下面 深入研究的目的是将这些细胞用于再生医学。 此外，很明显肿瘤生长通常从茎中脱发 细胞或其增殖后代。成年干细胞的一个重要人群是 肠上皮干细胞。我们最近在果蝇成人中发现 后肠干一个干细胞系统，表现出与哺乳动物相似的高度相似之处 肠道干细胞，但同时进行遗传分析非常简单 并在发展上。果蝇后肠干细胞仅限于 后肠，后肠增殖区（HPZ）。在HPZ中，自我更新， 增殖和分化由四个信号通路的局部来源控制， Wnt/Wing无刺猬，刺猬，Notch和Jak/Stat Pathway。在拟议的项目中我们 将解决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个方面（细胞 循环？粘附？迁移？多能吗？）他们每个人都可以控制吗？此外， 果蝇肠道的快速发展和相对简单性为我们提供了 调查何时以及如何具有其特殊信号属性的机会 在开发过程中。最后，我们想筛选成人茎的新基因 细胞增殖。我们的总体目标是将Fly HPZ系统的知识提高到一个 学位使得制定其他，具体且易于翻译 研究计划，使用Fly Hindgut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.

• 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

A novel tissue in an established model system: the Drosophila pupal midgut.

• DOI: 10.1007/s00427-011-0360-x
• 发表时间: 2011-06
• 期刊: Development genes and evolution
• 影响因子: 2.4
• 作者: Takashima S;Younossi-Hartenstein A;Ortiz PA;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