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：
10188126
负责人：
Jiang Chang
金额：
$ 18.94万
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 2023-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10188126
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 Surface System Tamoxifen Testing Time Tissues Transgenic Mice Vision 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，大小为30-130nm。它们含有 DNA 片段、mRNA 和蛋白质，并作为一种新的信使出现，促进细胞、组织和器官之间的串扰。跟踪这些小细胞外囊泡的分布和动态性质，并量化它们的动力学是基本的。迫切需要开发一种敏感且非侵入性的内源性跟踪系统外泌体；这样的系统将为探索外泌体的正常生物学功能提供有力的工具。为了满足这样的需求，提出了一种独特的外泌体报告小鼠，通过它来揭示通讯生理条件下器官/组织或细胞之间的内源性外泌体网络并研究正常情况外泌体生物学。改良的生物发光报告基因将被敲入小鼠体内，这将提供超灵敏的稳定的标签和跟踪系统。记者的特异性诱导将在心肌细胞中进行测试心脏成纤维细胞作为两个例子。发光信号将被非侵入性地检测。总之，该研究将提供一种强大且多功能的遗传小鼠模型，以实现定位跟踪、量化几乎任何组织、器官或细胞谱系的内源性外泌体。这所提出的基因小鼠优于目前的离体和体内标记。