Post-embryonic neural crest-derived progenitors in zebrafish during development and maintenance of adult phenotypes

斑马鱼胚胎后神经嵴衍生祖细胞在成年表型的发育和维持过程中

• 批准号: 10348691
• 负责人: Megan Rihab Sayyad
• 金额: $ 6.64万
• 依托单位: UNIVERSITY OF VIRGINIA
• 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 2023-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10348691
• 关键词: Ablation; Address; Adolescent; Adult; Anatomy; Animals; Biological Models; Cell Differentiation process; Cell Fate Control; Cell Lineage; Cells; Complex; Data; Development; Developmental Biology; Embryo; Embryonic Development; Fishes; Future; Ganglia; Genomic approach; In Situ Hybridization; Individual; Injury; Investigation; Knowledge; Label; Laboratories; Larva; Location; Maintenance; Mediating; Natural regeneration; Neural Crest; Neural Crest Cell; Neuroglia; Neurons; Pattern; Peripheral Nerves; Peripheral Nervous System; Phenotype; Pigmentation physiologic function; Pigments; Population; Regenerative Medicine; Regenerative response; Reserve Cell; Role; Schwann Cells; Series; Skeleton; Skin; Specific qualifier value; System; Testing; Tissues; Undifferentiated; Vertebrates; Work; Zebrafish; blastomere structure; career; cell type; developmental genetics; experience; experimental study; genetic approach; in vivo; insight; mature animal; melanocyte; progenitor; programs; regeneration following injury; single-cell RNA sequencing; spinal nerve posterior root; stem cell biology; stem cell therapy; stem cells; tissue injury; training opportunity; transcriptomics

PROJECT SUMMARY/ABSTRACT Cell fate programs in the embryo are increasingly well understood, but little is known about those that mediate post-embryonic development. Nevertheless, such programs are essential to the formation of adult phenotypes. As an animal grows and develops, persisting progenitor cells differentiate to produce new tissues or to contribute to the expansion of patterns initiated in the larval stages. These post-embryonic progenitor populations are not well studied, and a focused examination is critical in our efforts to understand how adult phenotypes arise. The neural crest (NC) is an embryonic population of cells uniquely present in vertebrates that gives rise to a diverse range of cell types. It has proven to be an exceptional model system for investigating cell lineage and the dynamic controls of cell fate. Whereas much is known about the NC and the roles of NC cells in embryogenesis, post-embryonic progenitor cells derived from the NC have been far less studied. Prior work in zebrafish has shown that post-embryonic NC-derived progenitors differentiate into various cell types including pigment cells and glia. Outstanding questions about these cells concern their anatomical niches, their range of fates during development and how these fates are specified, and their normal roles and differentiative potential in adults, particularly in the context of regeneration. To address these issues, I have devised a series of experiments in zebrafish. In Aim 1, I will investigate the role of NC-derived progenitors (NCPs) in larva-to-juvenile fish, focusing primarily on identifying their anatomical location(s) and fate(s). This work will involve mapping single-cell expression data anatomically to locate presumptive niches of progenitor populations, as well as single-cell fate mapping in vivo. In Aim 2, I will examine the role of NCPs in maintenance of the adult form and the potential of these cells in the context of regeneration using fate mapping and single-cell transcriptomics. The proposed analyses will expand our knowledge of cell fate programs in post-embryonic NC-derived cells and will support future research in stem cell therapeutics and regenerative medicine.

项目总结/摘要 胚胎中的细胞命运程序越来越清楚，但对那些介导的程序知之甚少。 胚后发育尽管如此，这些程序对于成人表型的形成至关重要。 随着动物的生长和发育，持续存在的祖细胞分化产生新的组织或 有助于扩大在幼虫阶段开始的模式。这些胚胎后祖细胞 人口没有得到很好的研究，重点检查是至关重要的，在我们的努力，以了解成年人如何 表型出现。 神经嵴（NC）是脊椎动物中唯一存在的胚胎细胞群， 多种细胞类型。它已被证明是研究细胞谱系的特殊模型系统， 对细胞命运的动态控制尽管对NC和NC细胞在肿瘤中的作用已经有了很多了解， 胚胎发生，衍生自NC的胚胎后祖细胞的研究少得多。以前的工作 斑马鱼已经显示胚胎后NC衍生的祖细胞分化成各种细胞类型，包括 色素细胞和神经胶质。关于这些细胞的悬而未决的问题涉及它们的解剖学小生境、它们的细胞范围 发育过程中的命运以及这些命运是如何指定的，以及它们的正常作用和分化潜力 在成人中，特别是在再生的背景下。 为了解决这些问题，我在斑马鱼身上设计了一系列实验。在目标1中，我将研究 NC衍生的祖细胞（NCPs）在幼鱼到幼鱼中的作用，主要集中在识别其解剖结构上， 地点和命运。这项工作将涉及映射单细胞表达数据解剖定位 祖细胞群体的假定小生境，以及体内单细胞命运作图。在目标2中，我将 检查NCP在维持成人形式中的作用以及这些细胞在以下背景下的潜力： 使用命运作图和单细胞转录组学进行再生。拟议的分析将扩大我们的 胚胎后NC衍生细胞的细胞命运程序的知识，并将支持未来的干细胞研究 细胞疗法和再生医学。