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

细胞如何获得它们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，这个问题变得更加重要。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。这种潜能与它们的起源组织密切相关。在这个项目中，秀丽隐杆线虫的生殖器官被用作定义器官身份的遗传决定因素的模型。秀丽隐杆线虫生殖器官的所有体细胞组织都来源于两个体细胞性腺前体细胞。sgp经过一系列细胞分裂，在女性器官中产生5个成熟组织，在男性器官中产生4个成熟组织。产生这些特殊细胞类型的潜力在sgp出生时就被赋予了；它们的姐妹细胞在它们出生后不久就会分化。分子、生化和遗传实验的结合将用于将新鉴定的基因纳入器官鉴定的遗传模型，并确定SGP鉴定的关键早期调节因子。这项工作的结果将是对器官身份和多能性的遗传控制有更全面的了解，这有可能对包括人类干细胞在内的所有干细胞的基本认识产生重大影响。本研究项目的一个组成部分是开发一门高级本科遗传学实验课程，向学生介绍探究式研究。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参与该项目的研究。

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.