Novel Activators of Regeneration in Muller glia

穆勒胶质细胞再生的新型激活剂

基本信息

批准号：
9340183
负责人：
EDWARD M LEVINE
金额：
$ 63.51万
依托单位：
VANDERBILT UNIVERSITY MEDICAL CENTER
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-09-01 至 2019-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9340183
关键词：
Address Affinity Affinity Chromatography Alpha Cell Animal Model Area Behavior Biological Models Cell Cycle Proteins Cell Separation Cells Collaborations Cyclin-Dependent Kinase Inhibitor Data Disease Eye Fishes Genetic Goals Human Injectable Injury Intervention Knowledge Label Laboratories Membrane Messenger RNA MicroRNAs Muller&apos s cell Mus Natural regeneration Nuclear Pathology Pathway interactions Pharmacology Photoreceptors Population Preparation Proliferating Property Proteins Proteomics Protocols documentation RNA Reagent Records Regenerative response Reporter Research Retina Retinal Scientist Signal Transduction Source Stem cells Techniques Testing Therapeutic Thiouracil Vesicle Work Zebrafish adult stem cell base cell type comparative exosome gabazine gamma-Aminobutyric Acid in vivo innovation migration mouse model neoplastic cell neurotransmitter uptake next generation sequencing novel novel strategies prevent public health relevance receptor regenerative repaired retinal rods teleost fish transcription factor transcriptome transcriptome sequencing transcriptomics

项目摘要

Project Summary: Novel Activators of Regeneration in Müller Glia Müller glia are the predominant source of regenerative repair in the fish retina, but this is not the case in humans, where Müller glia respond to injury, pathology, or degeneration by becoming reactive, and, in many cases, gliotic. Recent research in non-regenerative mammalian model systems, such as the mouse, suggests that Müller glia could be pushed down a regenerative pathway, but bona-fide regeneration and repair will involve factors and protocols that are not yet identified. To address this gap in knowledge, we propose three projects that focus on the proliferative and neurogenic properties needed for regeneration. In the first project, we will develop a regeneration-priming protocol for mouse Müller glia through modulation of neurotransmitter uptake and inhibition of p27Kip1, a cell cycle protein that prevents properties associated with reactivity and regeneration in Müller glia. In the second project, we will perform a screen using exosomes to discover candidate exosomes and their constituent proteins and/or RNAs that stimulate regenerative properties in zebrafish and mouse Müller glia. In the third project, we will develop thiouracil tagging combined with RNA sequencing to capture the transcriptomes of Müller glia in selected states of regeneration based on our work from the first two projects. The culmination of this work will yield new factors for promoting regeneration and provide proof-of-concept for exosome-based delivery of factors as a therapeutic strategy.

项目摘要：穆勒胶质细胞再生的新型激活剂米勒神经胶质细胞是鱼类视网膜再生修复的主要来源，但在鱼类视网膜中情况并非如此人类中，米勒神经胶质细胞通过变得反应性来对损伤、病理或退化做出反应，并且在许多情况下最近对非再生哺乳动物模型系统（例如小鼠）的研究表明。米勒神经胶质细胞可以被推向再生途径，但真正的再生和修复将涉及尚未确定的因素和协议为了解决这一知识差距，我们提出了三个建议。专注于再生所需的增殖和神经源特性的项目在第一个项目中，我们将通过调节神经递质开发小鼠穆勒神经胶质细胞的再生启动方案 p27Kip1 的摄取和抑制，p27Kip1 是一种细胞周期蛋白，可防止与反应性和相关性相关的特性在第二个项目中，我们将使用外泌体进行筛选来发现。候选外泌体及其组成蛋白和/或RNA刺激再生特性在第三个项目中，我们将开发与RNA结合的thouracil标签。根据我们的工作，进行测序以捕获选定再生状态下穆勒胶质细胞的转录组这项工作的高潮将产生促进再生和发展的新因素。为基于外泌体的因子递送作为治疗策略提供概念验证。