Cellular and molecular dissection of a stem cell niche in a marine invertebrate

海洋无脊椎动物干细胞生态位的细胞和分子解剖

• 批准号: 2316882
• 负责人: Elaine Seaver
• 金额: $ 76万
• 依托单位: University of Florida
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-07-01 至 2026-06-30
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2316882&HistoricalAwards=false
• 关键词: Cellular; molecular; dissection; stem; cell

Stem cells have a unique ability to produce new cells to replace aging or injured tissues. Many animals distributed across the tree of life have excellent regeneration abilities, whose regeneration success depends in part on the presence of resident stem cells. In these animals, the population of stem cells can generate multiple tissues and cell types, and it is important to build an understanding of how these stem cells are regulated in natural environment of the animal (versus in a dish in the lab). A putative stem cell niche was identified in the marine worm Capitella teleta, an animal that not only has robust regenerative abilities but also renews its germline, the cells that form eggs in females and sperm in males, throughout life. This finding offers a unique opportunity to investigate the relationship between germline and somatic stem cells. Capitella has numerous experimental advantages including optical clarity, a slow evolving and annotated genome, and available tools to manipulate gene function. Outreach activities include laboratory training of the next generation of researchers and development of a life-long learning module to inform adults on empirically based science and environmental stewardship. The proposed study emphasizes the value of studying a diversity of animals to understand major trends in animal evolution.Adult stem cells function during tissue homeostasis, growth, and repair in response to injury. In some contexts, stem cells reside in specific locations within the body and in others, an entire tissue or body functions as a supportive environment for stem cells. This work in the annelid Capitella teleta will explore the relationship between germline and somatic stem cells. Capitella has favorable characteristics for in vivo studies of stem cell biology, including a sequenced genome, a stereotypic cleavage program and associated fate map and availability of functional genomic tools. Through expression analysis of multipotency cell program genes, a putative stem cell niche was identified in Capitella with a discrete location within the body. The proposed work seeks to address the hypothesis that this putative stem cell niche can generate both somatic and germline cells. The function of the cluster will be investigated through direct experimental manipulations, live cell imaging, and functional genomic approaches. Cellular responses to injury will be compared with behavior of cells in this cluster in steady state conditions. The proposed experiments will help unravel the molecular regulation underlying the evolutionary relationship between somatic and germline stem cells. These studies will also provide insight into mechanistic differences that regulate localized stem cell populations in somatic and germ line microenvironments versus dispersed stem cell populations present in other animals. The broader impacts include development of life-long learning modules for adults to engage and educate the growing Florida population on biodiversity and evolutionary concepts.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

干细胞具有产生新细胞以替代老化或受损组织的独特能力。许多分布在生命之树上的动物都具有出色的再生能力，其再生成功部分取决于常驻干细胞的存在。在这些动物中，干细胞群体可以产生多种组织和细胞类型，重要的是要了解这些干细胞在动物的自然环境中（与实验室中的培养皿相比）如何调节。在海洋蠕虫Capitella teleta中发现了一个假定的干细胞生态位，这种动物不仅具有强大的再生能力，而且还能更新其生殖系，即在雌性中形成卵子和在雄性中形成精子的细胞。这一发现提供了一个独特的机会来研究生殖系和体干细胞之间的关系。Capitella具有许多实验优势，包括光学清晰度，缓慢进化和注释的基因组，以及操纵基因功能的可用工具。外联活动包括对下一代研究人员进行实验室培训，以及开发一个终身学习模块，向成年人介绍以经验为基础的科学和环境管理。这项研究强调了研究动物多样性的价值，以了解动物进化的主要趋势。成体干细胞在组织稳态，生长和修复损伤中发挥作用。在某些情况下，干细胞驻留在体内的特定位置，而在其他情况下，整个组织或身体充当干细胞的支持环境。 这项工作在环节动物Capitella teleta将探讨生殖系和体干细胞之间的关系。Capitella具有用于干细胞生物学的体内研究的有利特征，包括测序的基因组、定型切割程序和相关的命运图以及功能基因组工具的可用性。通过对多能性细胞程序基因的表达分析，在Capitella中鉴定出一个假定的干细胞小生境，其在体内具有离散的位置。拟议的工作旨在解决这一假设，即这种假定的干细胞龛可以产生体细胞和生殖细胞。通过直接的实验操作，活细胞成像和功能基因组学的方法来研究集群的功能。将对损伤的细胞反应与稳态条件下该簇中细胞的行为进行比较。拟议的实验将有助于解开体细胞和生殖干细胞之间进化关系的分子调控。这些研究还将提供对调节体细胞和生殖系微环境中的局部干细胞群体与其他动物中存在的分散干细胞群体的机制差异的深入了解。更广泛的影响包括终身学习模块的成人参与和教育不断增长的佛罗里达人口的生物多样性和进化概念的发展。这个奖项反映了NSF的法定使命，并已被认为是值得通过使用基金会的智力价值和更广泛的影响审查标准进行评估的支持。