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.

抽象的 这笔赠款的目标是适应当代单细胞分辨率和基因组操作 利用殖民海鞘物种 Botryllus 独特的再生生物学的工具 施洛塞里。我们回应 ORIP 的 FOA 的既定目标是创造新的和 干细胞生物学和再生的创新模型，Botryllus 拥有经过验证的轨迹 创新研究的记录和丰富的生物学知识将通过这些新的技术而变得可用 工具。海鞘是脊索动物，被认为是现存与海鞘最近的亲戚 脊椎动物。像玻璃海鞘这样的物种已经成为剖析早期进化步骤的有力模型。 脊索动物胚胎发生由于其相对简单和快速发育，并且具有许多共同点 脊索动物特有的特征，包括细胞规范的早期机制，以及 多种组织的克隆起源。除了这种密切的系统发育关系之外， 海鞘物种是群体性的，它们的生长不是通过体积的增加，而是通过一个过程 再生——整个身体——包括所有心血管、神经、内分泌和 种系组织 - 会再生，在葡萄孢属中，这种情况每周都会同步发生 时尚，提供了一种新的模型来研究脊索动物所有主要器官系统的再生。 殖民海鞘是唯一能够再生每个组织和器官的脊索动物。 它们的身体和独特的生活史特征使Botryllus成为潜在的杰出模型 对于这些研究。