Epigenetic Regulation of the Embryonic Germ Line

胚胎种系的表观遗传调控

• 批准号: 7406748
• 负责人: William G. KELLY
• 金额: $ 25.4万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-05-01 至 2010-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7406748
• 关键词: ATP phosphohydrolase; Address; Adult; Affect; Animal Genetics; Animal Model; Architecture; Biochemical; Biological Models; Caenorhabditis elegans; Cell Lineage; Cell Maintenance; Cell Survival; Cells; Chromatin; Chromatin Modeling; Chromatin Structure; Complex; Defect; Development; Disease; Drosophila genus; Embryo; Embryonic Development; Epigenetic Process; Foundations; Generations; Genes; Genetic; Genetic Transcription; Genome; Germ Cells; Germ Lines; Histocompatibility Testing; Histone H3; Histones; Homologous Gene; Human; Lead; Maintenance; Mediating; Mutation; Nematoda; Nucleosomes; Numbers; Organism; Pathway interactions; Phenocopy; Play; Pluripotent Stem Cells; Prevention; Process; Proteins; Regulation; Regulatory Pathway; Repression; Research Personnel; Role; Signal Transduction; Soil; Stem cells; Structure; Structure of primordial sex cell; Zinc Fingers; amine oxidase; base; cell growth; cell type; chromatin remodeling; gene repression; insight; neoplastic cell; notch protein; pluripotency; prevent; programs; reproductive; research study; tissue regeneration

DESCRIPTION (provided by applicant): Pluripotent stem cells have the natural capacity to generate multiple types of tissues in an organism. Germ cells give rise to all structural and reproductive lineages at each generation, and may therefore be considered the ultimate form of pluripotent stem cell. Understanding the mechanisms that maintain embryonic germ cell pluripotency will likely provide understanding of similar mechanisms used to maintain somatic stem cell lineages. Pluripotency is an essential feature of germ cells and its maintenance is tied to germ cell viability. Genome-wide transcriptional repression has been observed to play a predominant role in germ line maintenance in a number of species, including the soil nematode C. elegans. C. elegans is an animal genetic model system that has provided key insights into the regulation and mechanisms of a number of conserved processes that, when disturbed in humans, cause disease. We use this model organism to study germ cell development, and have identified a highly conserved mode of germ line maintenance that involves establishment and maintenance of specific chromatin architecture. This process is essential for germ cell survival and maintenance, and therefore is essential for maintaining a pluripotent cell type. Understanding how the unique germ cell chromatin architecture is established and maintained will be key to our understanding of germ cell maintenance. This will provide insights into how transcriptional programs can be regulated or repressed at the level of the genome, which could prove useful for targeting tumor cells for growth repression. This could also provide a better foundation for understanding how pluripotency is achieved and hopefully lead to therapies involving somatic stem cells.

描述（由申请人提供）：多能干细胞具有在生物体中产生多种类型组织的天然能力。生殖细胞在每一代产生所有的结构和生殖谱系，因此可以被认为是多能干细胞的最终形式。了解维持胚胎生殖细胞多能性的机制将可能提供用于维持体干细胞谱系的类似机制的理解。多能性是生殖细胞的基本特征，其维持与生殖细胞活力有关。全基因组转录抑制在包括土壤线虫C.优美的C.线虫是一种动物遗传模型系统，它为许多保守过程的调节和机制提供了关键的见解，这些过程在人类中受到干扰时会导致疾病。我们使用这种模式生物来研究生殖细胞发育，并确定了一个高度保守的生殖系维护模式，涉及建立和维护特定的染色质结构。这一过程对于生殖细胞的存活和维持至关重要，因此对于维持多能细胞类型至关重要。了解独特的生殖细胞染色质结构是如何建立和维持的，将是我们理解生殖细胞维持的关键。这将提供关于转录程序如何在基因组水平上被调节或抑制的见解，这可能被证明对靶向肿瘤细胞进行生长抑制有用。这也可以为理解多能性是如何实现的提供更好的基础，并有望导致涉及体干细胞的治疗。