Characterizing the molecular regulators of stem cell populations during homeostasis and regeneration in Hydractinia, an emerging cnidarian research organism

表征水螅（一种新兴的刺胞动物研究生物体）稳态和再生过程中干细胞群的分子调节因子

• 批准号: 10478237
• 负责人: Christine Schnitzler
• 金额: $ 36.5万
• 依托单位: UNIVERSITY OF FLORIDA
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-01 至 2025-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10478237
• 关键词: Animal Experimentation; Animal Model; Animals; Cell Cycle; Cell Maintenance; Cells; Characteristics; Cnidaria; Development; Embryo; Event; Gene Expression Profiling; Generations; Genes; Genetic; Genome; Genomics; Goals; Growth; Homeostasis; Human; Hydrozoa; Invertebrates; Life; Maintenance; Mediating; Molecular; Natural regeneration; Nature; Normal tissue morphology; Organism; Population; Public Health; Regenerative Medicine; Regenerative capacity; Regenerative research; Research; Resources; Role; System; Time; Tissues; Transgenic Organisms; Vision; Work; base; gain of function; in vivo; regenerative; regenerative biology; single-cell RNA sequencing; stem cell function; stem cell population; stem cell self renewal; stem cells; tissue regeneration; tool; trait

Project Summary/Abstract: Overview of research: Research in my lab centers on marine regenerative biology and specifically on stem cell-mediated regeneration. Our research organism is the hydrozoan cnidarian Hydractinia symbiolongicarpus. Hydractinia is a colonial invertebrate that has evolved a remarkable stem cell system and an astonishing capacity for regeneration. This animal can regenerate all of its tissues throughout life, owing to the constant turnover of its migratory stem cells, known as i-cells. The i-cell population is functionally heterogeneous and recently, fast-cycling and slow-cycling ‘quiescent’ sub-populations of i-cells have been identified based on cell cycle characteristics. Together with collaborators, we recently sequenced and assembled the Hydractinia genome and have created fluorescent transgenic lines. The genomic resources we have created and the functional molecular tools that currently exist and are under development for gene loss- and gain-of-function experimentation are enabling a new era of Hydractinia research. Goals for next five years: Our first goal is to successfully isolate purified sub-populations of stem cells from Hydractinia. Once this is achieved, we will work to characterize the essential nature of the i-cell sub- populations using global single cell transcriptional profiling (single cell RNAseq), followed by careful functional genetic experimentation. We will aim to characterize the underlying mechanisms governing i-cell maintenance during homeostasis and deployment during regeneration. Overall vision: My overall vision is to significantly contribute to the field of regenerative medicine by establishing Hydractinia as an exciting new research organism for stem cell and regeneration research. Hydractinia has a combination of traits such as small size, transparency, short generation times, and easy access to embryos that make it ideal for model organism development. As one of a handful of highly regenerative animals that can be easily cultured, spawned, and manipulated in the lab, Hydractinia is poised to help us unlock the mysteries and mechanisms that govern stem cell quiescence and proliferation. Our studies will characterize stem cell function in the contexts of normal tissue homeostasis and throughout the diverse molecular and cellular events of regeneration. One major long-term goal is to provide a means to specifically target and activate quiescent stem cells in vivo to enhance tissue regeneration that may ultimately be applied to human cells.

项目概要/摘要： 研究概述：我实验室的研究集中在海洋再生生物学，特别是干细胞 细胞介导再生我们的研究生物体是水螅刺胞动物Hydractinia symbiolongarpus。 Hydractinia是一种群体无脊椎动物，已经进化出了一个显着的干细胞系统， 再生能力。这种动物一生中可以再生所有的组织， 它的迁移干细胞的周转，被称为i细胞。i细胞群在功能上是异质的， 最近，基于细胞分类鉴定了I细胞的快速循环和慢速循环“静止”亚群。 周期特征我们与合作者一起，最近对Hydractinia进行了测序和组装， 基因组，并创造了荧光转基因线。我们创造的基因组资源 目前存在的和正在开发的基因功能丧失和获得的功能分子工具 实验开启了海葵研究的新纪元。 下一个五年的目标：我们的第一个目标是成功分离纯化的干细胞亚群， 水螅一旦实现这一目标，我们将努力表征i细胞亚细胞的基本性质， 使用全局单细胞转录谱分析（单细胞RNAseq），然后使用仔细的功能性分析， 基因实验我们的目标是描述控制i细胞维持的潜在机制 在体内平衡和再生期间展开。 总体愿景：我的总体愿景是通过以下方式为再生医学领域做出重大贡献 建立Hydractinia作为一个令人兴奋的新的研究生物体干细胞和再生研究。 水螅具有多种特性，如体积小，透明，世代时间短， 获得胚胎，使其成为模式生物发育的理想选择。作为少数几个 再生动物，可以很容易地培养，产卵，并在实验室操纵，Hydractinia准备 帮助我们解开控制干细胞静止和增殖的奥秘和机制。我们的研究 将在正常组织稳态的背景下和整个不同的组织中表征干细胞功能。 再生的分子和细胞事件。一个主要的长期目标是提供一种方法， 在体内靶向并激活静止干细胞以增强组织再生 到人体细胞。