Diet and Germline Progenitors

饮食和种系祖细胞

• 批准号: 10160935
• 负责人: E. Jane Albert Hubbard
• 金额: $ 42.38万
• 依托单位: NEW YORK UNIVERSITY SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-06-01 至 2025-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10160935
• 关键词: Address; Animals; Biological Models; Biology; Caenorhabditis elegans; Cell Differentiation process; Cell Proliferation; Cell physiology; Cells; Complex; Cues; Degenerative Disorder; Development; Diet; Dietary Component; Dietary Factors; Eating; Ensure; Escherichia coli; Fertility; Generations; Germ Cells; Growth; Human; Impairment; Insulin; Internet; Laboratories; Link; Maintenance; Metabolic; Metabolism; Modeling; Nature; Nutrient; Nutritional; Organ; Organism; Parasites; Process; Proliferating; Signal Pathway; Signal Transduction; Tissues; Transforming Growth Factor beta; base; cancer stem cell; cell behavior; dietary; dietary manipulation; genetic manipulation; in vivo; progenitor; response; stem cell biology; stem cells

Organisms eat to live, and diet provides material for growth and maintenance. However, complex webs of nutrient-responsive signaling pathways ensure that nutrients are properly allocated and utilized to support cellular processes such as proliferation and differentiation, commensurate with the demands of developmental stage and organismal needs. We know that signaling in response to diet is key to functional provisioning of dietary components, since signaling pathways can be manipulated to overcome nutritional deficits that would otherwise impair these processes. However, despite the fundamental nature of diet and metabolic signaling, the identity of key dietary factors, how they trigger particular signaling pathways in vivo, and how they operate within organismal metabolism to regulate cell behavior are poorly understood. We are addressing this gap using C. elegans germline progenitor cells as a model system. Germ cells are exquisitely sensitive to diet, making them an ideal model. Stem and progenitor cells are important targets of diet-based signaling, since they must continuously maintain tissues and organs under changing conditions. C. elegans offers experimental advantages including facile genetic and dietary manipulation. In addition, the C. elegans laboratory diet, E. coli, is itself a genetically tractable organism. Using complementary candidate and unbiased approaches, this project will identify dietary components that drive progenitor accumulation. Dietary cues will be linked to specific known (insulin, TGF-beta and TOR) or yet-to-be-implicated signaling pathways and cellular response mechanisms. The project will also address how robust accumulation of germline progenitors, in response to parental diet, impacts subsequent generations. Due to the highly conserved nature of metabolism and nutrient-reponsive signaling across evolutionarily divergent organisms, our studies will contribute to the understanding of fundamental mechanisms that maintain proliferating pools of cells, with possible implications in humans for fertility, development, degenerative diseases, cancer, stem cell biology, and parasite biology.

生物体吃饭是为了生存，饮食为生长和维持提供物质。然而，复杂 营养响应信号通路网络确保营养得到正确分配和利用 支持增殖和分化等细胞过程，与需求相称 发育阶段和机体需要。我们知道，响应饮食的信号是关键 膳食成分的功能性供应，因为可以操纵信号通路来克服 否则会损害这些过程的营养缺乏。然而，尽管有基本 饮食和代谢信号的性质、关键饮食因素的身份、它们如何触发特定的 体内信号通路，以及它们如何在有机体代谢中发挥作用来调节细胞行为 人们了解甚少。我们正在使用秀丽隐杆线虫种系祖细胞作为解决这一差距 模型系统。生殖细胞对饮食极其敏感，这使它们成为理想的模型。茎和 祖细胞是基于饮食的信号传导的重要目标，因为它们必须持续维持 组织和器官处于变化的条件下。线虫提供的实验优势包括 简单的遗传和饮食控制。此外，线虫实验室饮食大肠杆菌本身就是一种 遗传易驯化的有机体。该项目使用互补的候选者和公正的方法 将确定促进祖细胞积累的饮食成分。饮食线索将与特定的 已知（胰岛素、TGF-β 和 TOR）或尚未涉及的信号传导途径和细胞反应 机制。该项目还将解决生殖系祖细胞如何强劲积累的问题，以应对 父母的饮食，影响后代。由于新陈代谢的高度保守性 进化上不同的生物体之间的营养反应信号传导，我们的研究将有助于 了解维持细胞增殖池的基本机制，并可能 对人类生育、发育、退行性疾病、癌症、干细胞生物学和 寄生虫生物学。