Development of a Astroglia Maturation Gene Database

星形胶质细胞成熟基因数据库的开发

• 批准号: 8581796
• 负责人: LAKSHMANAN Krishnan IYER
• 金额: $ 8.25万
• 依托单位: TUFTS UNIVERSITY BOSTON
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-05-01 至 2015-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8581796
• 关键词: Affinity Chromatography; Alzheimer' s Disease; Amyotrophic Lateral Sclerosis; Astrocytes; Atlases; Biochemical Pathway; Biological; Brain; Buffers; Categories; Cerebrovascular Circulation; Circadian Rhythms; Clinical; Collaborations; Communication; Communities; Data; Databases; Development; Disease; Epilepsy; Functional disorder; Future; Gene Expression; Gene Expression Profile; Gene Expression Profiling; Genes; Glutamates; Human; Internet; Intervention; Ions; Libraries; Messenger RNA; Methods; Molecular; Mus; Nervous System Physiology; Neuraxis; Neurodegenerative Disorders; Neuroglia; Neurologic; Neurons; Neurosciences; Ontology; Parkinson Disease; Pathway interactions; Pharmaceutical Preparations; Play; Process; Protein Biosynthesis; RNA Splicing; Research; Resolution; Resources; Ribosomes; Role; Sensory Process; Sleep; Staging; Technology; Time; Transcript; Translating; Universities; Water; Yang; cell type; data mining; design; digital; gene interaction; genome database; in vivo; information framework; interest; nervous system disorder; neurotransmitter uptake; next generation; next generation sequencing; novel; postnatal; programs; public health relevance; synaptic function; synaptogenesis; therapy development; transcriptome sequencing; uptake

DESCRIPTION (provided by applicant): Recent studies have recognized the significant roles of astroglia (astrocytes) in central nervous system (CNS) functions including neurotransmitter uptake, water transport, control of cerebral blood flow, buffering of ions, control of neuronal synapse formation/function, sensory processing, circadian rhythms and sleep. Astroglia have also been implicated in several neurodegenerative diseases such as epilepsy, Alzheimer's disease (AD), Parkinson's disease (AD) and amyotrophic lateral sclerosis (ALS) and are considered to be potential targets for clinical intervention. However, how astrocytes become developmentally mature is not well understood. In parallel, previous gene expression profiling studies using microarrays have allowed the characterization and comparison of gene expression patterns for various CNS cell types including astroglia. However, microarrays, by design are limited by the bias of the probes and inability to detect uncharacterized transcripts. I addition, a detailed database of the astroglial developmental molecular changes, in particular, gene expression change and alternative transcript splicing, is currently not available. Built on our preliminary studies on employing BAC ALDH1L1 TRAP mice and next generation sequencing (NGS) technologies, we propose to generate a database resource of gene expression changes during astroglia maturation, by sequencing astrocyte translating mRNAs isolated from mouse cortex at different developmental stages in vivo. Further, the differential expression of transcripts and the extent of alternative transcripts of genes during the postnatal astrocyte development will be determined. In the secondary analysis, the gene expression changes at each time point of the development will also be analyzed to determine the enrichment of gene ontology categories, biochemical pathways and top enriched gene interaction sub- networks. The results of RNA-seq and secondary analysis will be compiled together with public annotations and integrated with other available expression data on astrocytes and made available to the neuroscience community via the web. It will be available for data mining that will facilitate functional studies of astrocytes and provide targets for clinial intervention in neurological disorders. This collaboration between a glia biologist (Dr. Yang) and a computational biologist (Dr. Iyer) is at the Neuroscience department of Tufts University with a vibrant and collaborative glia research program led by Dr. Phil Haydon and Dr. Rob Jackson.

描述(申请人提供)：最近的研究已经认识到星形胶质细胞在中枢神经系统(CNS)功能中的重要作用，包括神经递质摄取、水运输、控制脑血流量、缓冲离子、控制神经元突触形成/功能、感觉处理、昼夜节律和睡眠。星形胶质细胞还与癫痫、阿尔茨海默病(AD)、帕金森病(AD)和肌萎缩侧索硬化症(ALS)等多种神经退行性疾病有关，被认为是临床干预的潜在靶点。然而，星形胶质细胞是如何发育成熟的还不是很清楚。同时，以前使用微阵列的基因表达谱研究已经允许描述和比较包括星形胶质细胞在内的各种类型的中枢神经系统细胞的基因表达模式。然而，微阵列的设计受到探针偏向和无法检测未鉴定转录本的限制。I此外，目前还没有关于星形胶质细胞发育分子变化的详细数据库，特别是基因表达变化和选择性转录剪接。在我们利用BAC ALDH1L1陷阱小鼠和下一代测序(NGS)技术的初步研究的基础上，我们建议通过对从体内不同发育阶段的小鼠大脑皮质分离的星形胶质细胞翻译的mRNAs进行测序，建立一个星形胶质细胞成熟过程中基因表达变化的数据库资源。此外，将确定在出生后星形胶质细胞发育过程中转录本的差异表达和基因选择性转录本的程度。在二次分析中，还将分析发育各个时间点的基因表达变化，以确定丰富的基因本体论类别、生化途径和顶级丰富的基因相互作用子网络。Rna-seq和二次分析的结果将与公共注释一起汇编，并与其他关于星形胶质细胞的现有表达数据整合在一起，并通过网络提供给神经科学界。它将用于数据挖掘，促进星形胶质细胞的功能研究，并为神经疾病的临床干预提供靶点。这是一位胶质生物学家(杨博士)和 一位计算生物学家(Iyer博士)在塔夫茨大学神经科学系，由Phil Haydon博士和Rob Jackson博士领导一个充满活力和合作的神经胶质研究项目。