Epigenetic Regulation of the Embryonic Germ Line

描述(申请人提供)：多能干细胞具有在生物体中生成多种组织的天然能力。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终极形式。了解维持胚胎生殖细胞多能性的机制可能有助于理解用于维持体细胞干细胞谱系的类似机制。多能性是生殖细胞的一个基本特征，它的维持与生殖细胞的活力息息相关。已观察到全基因组转录抑制在许多物种的种系维持中起主导作用，包括土壤线虫线虫。线虫是一个动物遗传模型系统，它为一些保守过程的调控和机制提供了关键的见解，这些过程在人类体内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的发育，并确定了一种高度保守的生殖系维持模式，包括建立和维持特定的染色质结构。这一过程对生殖细胞的生存和维持至关重要，因此对维持多能细胞类型也是必不可少的。了解独特的生殖细胞染色质结构是如何建立和维持的，这将是我们理解生殖细胞维持的关键。这将为如何在基因组水平上调节或抑制转录程序提供见解，这可能被证明对靶向肿瘤细胞生长抑制有用。这也可以为理解多能性是如何实现的提供更好的基础，并有望导致使用躯体干细胞的治疗。

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.