Profiling communication networks of endogenous exosomes

分析内源性外泌体的通讯网络

基本信息

批准号：
10394353
负责人：
Jiang Chang
金额：
$ 22.73万
依托单位：
TEXAS A&M UNIVERSITY HEALTH SCIENCE CTR
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-04-16 至 2025-03-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10394353
关键词：
Alleles Animals Area Biological Assay Biological Process Biology Bioluminescence Breeding CRISPR/Cas technology Cardiac Cardiac Myocytes Categories Cell Lineage Cells Communication DNA DNA cassette Development Drug or chemical Tissue Distribution Fibroblasts Fluorescent Dyes Funding Generations Genetic Heart Image In Vitro Intraperitoneal Injections Kinetics Knock-in Knock-in Mouse Label Location Luciferases Magnetic Resonance Measures Mediating Messenger RNA Methods Modeling Monitor Morphology Mus Mutation National Heart, Lung, and Blood Institute Nature Organ Physiological Pilot Projects Plasma Proteins Radioisotopes Reagent Reporter Reporter Genes Reporting Research Research Personnel Signal Transduction Strategic vision Surface System Tamoxifen Testing Time Tissues Transgenic Mice bioluminescence imaging exosome experimental study extracellular vesicles genome sequencing heart function improved in vivo in vivo imaging system intravenous injection mouse model mutant nanolabel nanoluciferase promoter success tool vector whole genome

项目摘要

PROJECT DESCRIPTION/ABSTRACT Exosomes are secreted small extracellular vesicles with the size 30-130nm. They contain DNA fragments, mRNAs and proteins, and emerge as a new category of messengers that facilitate cross-talk among cells, tissues, and organs. Tracking the distribution and dynamic nature of these small extracellular vesicles, and quantifying their kinetics are essential. A critical demand arises for the development of a sensitive and noninvasive tracking system for endogenous exosomes; such a system will provide a powerful tool for the exploration of the normal biological functions of exosomes. To meet such as a demand, a unique exosome reporter mouse is proposed, through which to reveal communication networks of endogenous exosomes among organs/tissues or cells in physiological conditions and investigate normal exosome biology. A modified bioluminescent reporter will be knocked in the mice, which will provide an ultra-sensitive and stable labeling and tracking system. The specific inductions of the reporter will be tested in cardiomyocytes and cardiac fibroblasts as two examples. The luminescent signaling will be detected non-invasively. In summary, the study will provide a powerful and versatile genetic mouse model to enable location tracking, quantifying endogenous exosomes derived from almost any tissues, organs or cell lineages. The proposed genetic mice are superior to the current ex vivo and in vivo labeling.

项目描述/摘要外泌体是分泌的小细胞外囊泡，尺寸为30-130nm。它们包含DNA片段，mRNA 和蛋白质，并成为促进细胞，组织和器官之间交叉对话的新类别。跟踪这些小细胞外囊泡的分布和动态性质，并量化其动力学基本的。对于内源性的敏感和无创的跟踪系统的开发产生了关键需求外泌体；这样的系统将为探索外泌体的正常生物学功能提供强大的工具。为了满足需求，提出了独特的外sos子记者鼠标在生理条件下器官/组织或细胞之间内源性外泌体网络并研究正常外泌体生物学。在小鼠中将敲打改良的生物发光记者，这将提供超敏感的以及稳定的标签和跟踪系统。记者的特定诱导将在心肌细胞和心脏成纤维细胞作为两个例子。发光信号传导将非侵入性检测到。总而言之，该研究将提供功能强大且通用的遗传小鼠模型，以实现位置跟踪，量化来自几乎所有组织，器官或细胞谱系的内源性外泌体。这提出的遗传小鼠优于当前的离体和体内标记。