Elucidating the genetic determinants of organ identity using the C. elegans reproductive organs as a model

使用线虫生殖器官作为模型阐明器官身份的遗传决定因素

• 批准号: 1314144
• 负责人: Laura Mathies
• 金额: $ 44.43万
• 依托单位: Virginia Commonwealth University
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-10-01 至 2015-07-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1314144&HistoricalAwards=false
• 关键词: Elucidating; genetic; determinants; organ; identity

How cells acquire their identity is a fundamental question in Developmental Biology and one that has gained additional importance in the era of stem cell biology. In order to harness the potential of adult stems cells, the genetic factors that give them their unique potential must be understood. This potential is intimately linked with their tissue of origin. In this project, the reproductive organs of the worm Caenorhabditis elegans are used as a model for defining the genetic determinants of organ identity. All somatic tissues of C. elegans reproductive organs derive from two somatic gonadal precursor cells (SGPs). The SGPs undergo a set of cell divisions to generate five mature tissues in the female organ or four mature tissues in the male organ. The potential to generate these particular cell types is imparted to the SGPs at their birth; their sister cells differentiate shortly after they are born. A combination of molecular, biochemical, and genetic experiments will be used to incorporate newly identified genes into a genetic model for organ identity and to identify critical early regulators of SGP identity. The outcome of this work will be a more complete understanding of the genetic controls of organ identity and multipotency, which has the potential to impact significantly the basic understanding of all stem cells, including human stem cells. An integral part of this research project is the development of an advanced undergraduate genetics lab course that will introduce students to inquiry-based research. In addition, this project will provide training for future US scientists, in that several undergraduate students, two graduate students, and one postdoctoral fellow will be engaged in conducting the research in this project.

细胞如何获得自己的身份是发育生物学的一个基本问题，在干细胞生物学时代也变得更加重要。为了利用成体干细胞的潜力，必须了解赋予它们独特潜力的遗传因素。这种潜力与它们的起源组织密切相关。在这个项目中，秀丽线虫的生殖器官被用作定义器官特性的遗传决定因素的模型。线虫生殖器官的所有体细胞组织都来自两个体细胞性腺前体细胞(SGP)。SGP经历一系列的细胞分裂，在雌性器官中产生5个成熟组织，或在雄性器官中产生4个成熟组织。产生这些特殊细胞类型的能力在SGP出生时就被赋予了；它们的姐妹细胞在出生后不久就分化了。分子、生化和遗传学实验的结合将被用于将新识别的基因整合到器官识别的遗传模型中，并识别SGP识别的关键早期调节因素。这项工作的结果将是对器官特性和多能性的遗传控制有更全面的理解，这有可能显著影响对包括人类干细胞在内的所有干细胞的基本理解。这项研究项目的一个组成部分是开发一门高级本科生遗传学实验室课程，该课程将向学生介绍基于探究的研究。此外，该项目还将为未来的美国科学家提供培训，将有几名本科生、两名研究生和一名博士后从事这一项目的研究。