Characterization of cellular and molecular components of intestinal niche

项目摘要/摘要 以快速和持续的周转为特征，肠道为 对自我更新和再生的细胞的研究，因此具有很大的再生前景 医药。研究对肠道干细胞的能力提供了重要的见解。 用于自我修复或修复以及持续维护和分化到所有不同的 肠道细胞类型。然而，需要大量的研究才能更好地理解如何 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(它们比 特定于干细胞)或由利基、微环境提供的误导信号 这有助于调节干细胞和祖细胞的行为。定义基本的蜂窝利基 指导干细胞和祖细胞增殖的组件和相关的关键信号 和区分将是治疗肠道疾病的创新和重要的一步 再生医学。 肠干细胞联盟(ISCC)的总体任务是确定利基的特征 支持健康和疾病中的肠道干细胞的组件，使用集成的、 多学科团队科学方法，以开发新的靶向疗法为愿景 肠道干细胞和支持利基，以再生和重建人类肠道。 为了实现体液疗法和组织疗法的临床前发展的最终目标， 本文提出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 动态平衡和应激状态，并在小鼠模型中定义它们，以提供 对人类器官生长的洞察。使用的方法包括散装和单细胞rna-seq。 分析、RNA显微镜、3D免疫荧光成像和3D有机物培养。

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.