Developing a new chordate model for stem cell biology and regeneration

开发用于干细胞生物学和再生的新脊索动物模型

• 批准号: 10373777
• 负责人: Anthony W De Tomaso
• 金额: $ 18.39万
• 依托单位: UNIVERSITY OF CALIFORNIA SANTA BARBARA
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-03-15 至 2024-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10373777
• 关键词: Adult; Animal Model; Animals; Biology; Blood Vessels; CRISPR/Cas technology; Cardiovascular system; Cell Differentiation process; Cell Lineage; Cells; Characteristics; Chordata; Databases; Development; Embryo; Embryonic Development; Endocrine; Gastrointestinal tract structure; Genes; Genome; Genomics; Germ Cells; Germ Layers; Glass; Goals; Grant; Heart; Human; Image; Invertebrates; Modeling; Modification; Natural regeneration; Nervous system structure; Neural Crest; Organ; Organism; Pattern; Peripheral Nervous System; Phylogenetic Analysis; Process; Regenerative pathway; Regenerative research; Reporter; Research; Resolution; STEM field; Series; Signal Transduction; Sister; Slide; Source; Stem cell transplant; Study models; Testing; Time; Tissues; Vertebrates; ascidian; asexual; body system; cardiac regeneration; cardiogenesis; cell regeneration; cell type; gene regulatory network; improved; innovation; life history; loss of function; notochord; novel; progenitor; regenerative; regenerative biology; response; self-renewal; single-cell RNA sequencing; stem cell biology; stem cell model; stem cells; tissue regeneration; tool; transcription factor

ABSTRACT The goal of this grant is to adapt contemporary single cell resolution and genomic manipulation tools to utilize the unique regenerative biology of the colonial ascidian species, Botryllus schlosseri. The FOA we are responding to from ORIP has as its stated goal to create new and innovative models for stem cell biology and regeneration, and Botryllus has a proven track record of innovative studies and a wealth of biology that will be made accessible with these new tools. Ascidians are chordates, and considered to be the closest living relatives to the vertebrates. Species such as Ciona have become powerful models in dissecting early steps in chordate embryogenesis due to their relative simplicity and rapid development, and share many chordate-specific features, including early mechanisms underlying cell specification, as well as clonal origins of multiple tissues. In addition to this close phylogenetic relationship, a subset of ascidian species are colonial, and grow, not by increasing in size, but via a process of regeneration- whereby entire bodies- including all cardiovascular, nervous, endocrine and germline tissues- are regenerated, and in Botryllus this occurs every week in a synchronized fashion, providing a novel model to study regeneration of all major organ systems in a chordate. Colonial ascidians are the only chordates with the ability to regenerate every tissue and organ in their body and unique life history characteristics make Botryllus a potentially outstanding model for these studies.

摘要 这项资助的目标是适应当代单细胞分辨率和基因组操作 利用殖民地海鞘物种的独特再生生物学的工具， 施洛塞里。我们正在回应的FOA来自ORIP，其既定目标是创造新的， 干细胞生物学和再生的创新模型，而Botryllus有一个经过验证的跟踪 创新研究的记录和丰富的生物学，将与这些新的访问 工具.海鞘是脊索动物，被认为是最接近生活的亲戚， 脊椎动物像玻璃海鞘这样的物种已经成为解剖早期阶段的有力模型， 脊索动物胚胎发生由于其相对简单和快速发展，并分享许多 脊索动物特有的特征，包括细胞特化的早期机制，以及 多种组织的克隆起源。除了这种密切的系统发育关系， 海鞘物种是殖民地，并增长，而不是通过增加大小，但通过一个过程， 再生-使整个身体-包括所有心血管，神经，内分泌和 生殖系组织-再生，在Botryllus这发生在每周同步 时尚，提供了一个新的模型，研究所有主要器官系统的再生脊索动物。 殖民海鞘是唯一的脊索动物的能力，再生的每一个组织和器官， 他们的身体和独特的生活史特征使波特吕勒斯成为一个潜在的杰出模型 进行这些研究。