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Functional Annotation of the Preimplantation Transcriptome

植入前转录组的功能注释

基本信息

批准号：
8833018
负责人：
Jesse Mager
金额：
$ 19.38万
依托单位：
UNIVERSITY OF MASSACHUSETTS AMHERST
依托单位国家：
美国
项目类别：
财政年份：
2014
资助国家：
美国
起止时间：
2014-04-06 至 2017-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8833018
关键词：
Bioinformatics Biological Models Bolus Infusion Cells Communities Competence Data Data Set Defect Derivation procedure Development Developmental Process Double-Stranded RNA Embryo Embryonic Development Epigenetic Process Event Exposure to Fertilization Gene Expression Gene Expression Profile Gene Expression Regulation Genes Genome Genomic Imprinting Goals Grant Health In Vitro Individual Knowledge Mammals Mediating Methods Microinjections Molecular Monitor Mus Nuclear Phenotype Placenta Play Process Publishing RNA Interference Regulation Reproductive Technology Research Role Screening Result Staging System Technology Therapeutic Time Tissues Transcript Work Zona Pellucida base blastocyst design embryo culture embryonic stem cell epigenetic regulation gene function hatching human disease implantation imprint improved in vitro Model in vivo in vivo Model interest knock-down loss of function mammalian genome novel preimplantation screening skills success tissue culture transcriptome sequencing zygote

项目摘要

DESCRIPTION (provided by applicant): Functional Annotation of the Preimplantation Transcriptome. The primary goal of this proposal is to elucidate the requirement of a large set of genes expressed during mammalian preimplantation development. After RNAi mediated loss of each gene function, we will assess morphological development, lineage specification, epigenetic regulation of genome imprinting and embryonic stem cell derivation potential. This work will extend a pilot RNAi screen that we have performed (~500 genes) in order to establish conditions for this transcriptome-wide effort. Currently there exist sufficient data sets such that we will not need to determine which genes are expressed ourselves - but can use the work of other groups in order to launch directly towards our goal of functional annotation of the preimplantation transcriptome. Our system capitalizes on the dynamic genome reprogramming that occurs during the first few days post-fertilization. Our approach uses mouse embryos as an in vivo model system and monitors early developmental events and genomic imprinting. Our approach provides a robust and efficient method towards identification of novel epigenetic regulatory mechanisms as well as functional requirements during development and we are uniquely poised to carry out the proposed work. In addition to the bolus of basic scientific knowledge our data will provide, our proposal is highly relevant for understanding the evidence that even short-term exposure to in vitro culture during preimplantation can have dire epigenetic consequences. Perhaps even more relevant are numerous examples of epigenetic defects in embryos and placentas of individual mammals generated through the use of artificial reproductive technologies. Understanding the basic molecular machinery that regulates epigenetic events during preimplantation is of critical importance if we are to improve current practice as well as to design therapeutic approaches for the many human disease states with epigenetic mis-regulation of gene expression.

描述（由申请人提供）：植入前转录组的功能注释。本研究的主要目的是阐明哺乳动物着床前发育过程中大量基因表达的需求。在RNAi介导的每个基因功能缺失后，我们将评估形态发育、谱系规范、基因组印迹的表观遗传调控和胚胎干细胞衍生潜力。这项工作将扩展我们已经进行的试点RNAi筛选（约500个基因），以便为这种转录组范围的努力建立条件。目前有足够的数据集