CELLULAR AND MOLECULAR STUDIES OF THE STEM CELL NICHE

干细胞生态位的细胞和分子研究

• 批准号: 8538969
• 负责人: Craig A Micchelli
• 金额: $ 31.9万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-09-01 至 2016-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8538969
• 关键词: Acids; Address; Adult; Age; Animal Model; Behavior; Biological; Biological Models; Biology; Cell Culture Techniques; Cell Lineage; Cell Maintenance; Cell Proliferation; Cell Survival; Cell Therapy; Cell model; Data; Disease; Drosophila genus; Environment; Epidermal Growth Factor Receptor; Epithelial; Epithelial Cells; Epithelium; Exhibits; Gastrointestinal tract structure; Gene Targeting; Genetic; Germ Lines; Goals; Health; Homeostasis; Human; Individual; Injury; Integrins; Intestines; Invertebrates; Knowledge; Laboratories; Life; Malignant Neoplasms; Mammals; Methods; Modeling; Molecular; Natural regeneration; Organism; Pathway interactions; Physiology; Proliferating; Reagent; Regenerative Medicine; Regulation; Regulatory Pathway; Research; Research Personnel; Resolution; Signal Pathway; Signal Transduction; Small Intestines; Specific qualifier value; Stem cells; Stomach; Testing; Tissues; Work; base; cell behavior; cell fate specification; cell type; cost effective; experience; human disease; improved; in vivo; insight; interest; notch protein; novel; programs; response; response to injury; stem cell biology; stem cell differentiation; stem cell niche; tool

DESCRIPTION (provided by applicant): Drosophila stem cell niches provide useful models for understanding mammalian stem cell behavior. Great progress has been made in defining principles that control constitutively active niches such as the germ line and intestine. However, the quiescent stem cell niche that can regenerate a tissue in response to injury is less well understood. Our studies have recently led to the identification of a novel gastric stem cell (GSSC) in the adult Drosophila stomach. GSSCs exhibit a number of unique behaviors. Significantly for this proposal, gastric stem cells are normally quiescent, but are rapidly induced to regenerate the entire gastric epithelium in response to tissue damaging injury. Our preliminary data indicate that GSSCs are controlled by conserved signaling pathways, which have been implicated in mammalian and invertebrate stem cell niches, including those found in the gastrointestinal tract. These observations raise the central hypothesis that epithelial regeneration in the stomach is achieved through a region-specific niche program, which adapts the GSSC to a unique stomach physiology. In Aim 1 we propose to test the mechanism of gastric stem cell maintenance in a quiescent niche. In Aim 2 we propose to characterize the signals that regulate gastric stem cell quiescence. In Aim 3 we propose to address the basis of cell fate specification in a tri-potent gastric lineage. These questions are currently difficult to address in mammals, as the principle gastric stem cells of the stomach have not yet been identified. Thus, we propose to use Drosophila as a model to dissect the mechanisms controlling a quiescent gastric stem cell niche.

描述（由申请人提供）：果蝇干细胞壁龛为理解哺乳动物干细胞行为提供了有用的模型。在确定控制生殖系和肠道等组成活性生态位的原则方面取得了巨大进展。然而，静止干细胞生态位在组织损伤后的再生能力尚不清楚。我们的研究最近在成年果蝇胃中发现了一种新的胃干细胞（GSSC）。gssc表现出许多独特的行为。值得注意的是，胃干细胞通常是静止的，但可以迅速诱导