Characterization of cellular and molecular components of intestinal niche

肠道生态位细胞和分子成分的表征

• 批准号: 10015255
• 负责人: LINHENG LI
• 金额: $ 41.25万
• 依托单位: STOWERS INSTITUTE FOR MEDICAL RESEARCH
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-30 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10015255
• 关键词: 3-Dimensional; American; Basement membrane; Cell Differentiation process; Cells; Child; Defect; Digestive System Disorders; Disease; Dissection; Epithelial; Epithelial Cells; Epithelium; Foundations; Goals; Growth; Health; Homeostasis; Human; Image; Immune; In Vitro; Inflammation; Intestinal Diseases; Intestines; Knowledge; Ligands; Light; Maintenance; Membrane; Methods; Michigan; Mission; Modeling; Molecular; Mucous Membrane; Mus; Myofibroblast; Natural regeneration; Organoids; Patient-Focused Outcomes; Population; Proliferating; Public Health; Quality of life; RNA; Regenerative Medicine; Regulation; Research; Research Project Grants; Science; Signal Transduction; Smooth Muscle; Stem Cell Development; Stress; Stromal Cells; Structure; Submucosa; System; Testing; Tissue Therapy; Villus; Vision; base; biological adaptation to stress; cell behavior; cell type; cost; healing; improved; innovation; insight; intestinal epithelium; mouse model; multidisciplinary; new therapeutic target; preclinical development; reconstitution; repaired; response; self-renewal; single-cell RNA sequencing; stem cell biology; stem cell proliferation; stem cells; therapy development

Project Summary/Abstract Characterized by rapid and continual turnover, the intestine provides an elegant system for the study of cells which self-renew and regenerate, and thus hold great promise for regenerative medicine. Studies have provided important insight regarding the capacity of intestinal stem cells for self-repair or healing as well as ongoing maintenance and differentiation into all the various intestinal cell types. However, considerable research is needed to better understand how to treat intestinal disorders. Many intestinal disorders are due to defects in the stem cells or progenitor cells (which are more specific than stem cells) or to misdirected signals provided by the niche, the microenvironment which helps to regulate stem and progenitor cell behavior. Defining the essential cellular niche components and the associated key signals that direct stem and progenitor cells to proliferate and differentiate will be an innovative and important step toward treating intestinal disorders with regenerative medicine. The overall mission of the Intestinal Stem Cell Consortium (ISCC) is to characterize the niche components that support intestinal stem cells in health and disease, using an integrated, multidisciplinary team science approach, with the vision of developing novel therapies targeting intestinal stem cells and supportive niche to regenerate and rebuild the human intestine. To achieve the ultimate goals of pre-clinical development of both humoral and tissue therapy, the research project proposed herein will contribute with the following specific aims: to characterize cellular components and molecular signals of the intestinal niche network under both homeostasis and stress conditions, and to define these in the mouse model to provide an insight into human organoid growth. Methods to be used include bulk and single cell RNA-seq analyses, RNA-scope, 3D immunofluorescent imaging, and 3D organoid culture.

项目总结/摘要 以快速和持续的周转为特征，肠为消化道提供了一个优雅的系统。 研究自我更新和再生的细胞，因此对再生有很大的希望。 药研究提供了关于肠道干细胞能力的重要见解 自我修复或愈合以及持续的维护和分化成所有的各种 肠细胞类型。然而，需要大量的研究来更好地了解如何 治疗肠道疾病。 许多肠道疾病是由于干细胞或祖细胞的缺陷（这些细胞在肠道中的数量更多）。 特异性比干细胞）或由小生境提供的错误信号，微环境 它有助于调节干细胞和祖细胞的行为。定义基本的细胞生态位 成分和相关的关键信号，指导干细胞和祖细胞增殖 和分化将是治疗肠道疾病的创新和重要的一步， 再生医学 肠道干细胞联盟（ISCC）的总体使命是描述 支持肠道干细胞在健康和疾病的组成部分，使用一个集成的， 多学科团队科学方法，旨在开发针对 肠道干细胞和支持性生态位可以再生和重建人类肠道。 为了实现体液和组织疗法临床前开发的最终目标， 本报告所建议的研究项目将有助于实现以下具体目标： 表征肠道生态位网络的细胞成分和分子信号， 稳态和应激条件，并在小鼠模型中定义这些，以提供 对人类类器官生长的深入了解使用的方法包括批量和单细胞RNA-seq 分析、RNA-显微镜、3D免疫荧光成像和3D类器官培养。