Identification of stem cells responsible for germline parasitism in Botryllus.

鉴定负责灰霉属种系寄生的干细胞。

• 批准号: 7689904
• 负责人: Michelle Marie Roux
• 金额: $ 5.01万
• 依托单位: UNIVERSITY OF CALIFORNIA SANTA BARBARA
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-08-30 至 2010-08-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7689904
• 关键词: Adult; Aging; Animals; Biological; Biological Assay; Blood; Candidate Disease Gene; Cell Differentiation process; Cell Ontogeny; Cells; Chordata; Data; Development; Developmental Process; Differentiation and Growth; Disease; Event; Expressed Sequence Tags; Genes; Genotype; Goals; Homing; In Situ Hybridization; Individual; Kinetics; Life Cycle Stages; Mediating; Methodology; Modeling; Molecular; Molecular and Cellular Biology; Natural regeneration; Outcome; Phenotype; Pluripotent Stem Cells; Population; Proliferating; Regenerative Medicine; Role; Small Interfering RNA; Somatic Cell; Stem cells; System; Testing; Tissues; Transplantation; ascidian; asexual; knock-down; life history; molecular marker; parasitism; programs; response to injury; self-renewal; stem; stem cell biology; stem cell population; tissue regeneration

DESCRIPTION (provided by applicant): Summary: Developmental programs that control cell differentiation, growth, tissue regeneration, aging, and those that are triggered in response to injury and disease, are all mediated by a pluripotent population of stem or progenitor cells. Although these cells control the most fundamental aspects of biology, the cellular and molecular mechanisms that define them and that control their expansion and differentiation is not well understood. The colonial ascidian, B. schlosseri, provides a unique model to study chordate stem cell biology. Regeneration is a major part of the life history of Botryllus: in a highly coordinated developmental process, Botryllus adults regenerate themselves, including all somatic tissues and the germline, every week. In addition, naturally occurring fusion events between individuals cause a population of primitive stem cells to mobilize, proliferate, differentiate and sometimes completely replace the germline of the host in an event called germline cell parasitism (gcp). Conserved and important aspects of stem cell biology, such as self-renewal capacity, homing or expansion, and differentiation kinetics must underlie the ability of a stem cell of one genotype to out compete a stem cell of another genotype. The overall objectives of this proposal are to use this system to prospectively isolate the cell(s) responsible for gcp, determine the cellular and molecular biological phenotype of these cell(s), and correlate those phenotypes with parasitic capability. We propose the following specific aims to accomplish the goals set forth in this study: Aim 1. To isolate and characterize the cells responsible for germline stem cell parasitism (gcp). Aim 2. To test functions of candidate stem cell markers during asexual regeneration and germline stem cell parasitism. Aim 3. To determine the ontogeny of cells responsible for germline stem cell parasitism Relevance: Characterization of stem cells in this unique chordate ancestor will help answer basic biological questions with applications in regenerative medicine.

描述（由申请人提供）：摘要：控制细胞分化，生长，组织再生，衰老以及响应损伤和疾病触发的程序，均由茎或祖细胞的多能量介导。尽管这些细胞控制着生物学的最基本方面，但定义它们的细胞和分子机制以及控制它们的扩展和分化的尚未得到很好的了解。殖民时期的海藻B. schlosseri提供了一个独特的模型来研究丘陵干细胞生物学。再生是Botryllus生活史的主要部分：在高度协调的发展过程中，Botryllus成年人每周都会重新生成，包括所有体细胞组织和种系。此外，个体之间的自然发生的融合事件会导致原始干细胞种群动员，增殖，分化，有时在称为生殖线细胞寄生虫（GCP）的事件中完全替代宿主的种系。干细胞生物学的保守和重要方面，例如自我更新能力，归巢或扩张以及分化动力学，必须是一种基因型干细胞的能力，使一个基因型的干细胞能够竞争另一种基因型的干细胞。该提案的总体目标是使用该系统将负责GCP的细胞隔离，确定这些细胞的细胞和分子生物学表型，并将这些表型与寄生能力相关联。我们提出以下特定目的，以实现本研究中规定的目标：目标1。隔离和表征负责生殖线干细胞寄生虫（GCP）的细胞。目标2。在无性再生和种系干细胞寄生虫中测试候选干细胞标记的功能。目的3。确定负责种系干细胞寄生虫相关性的细胞的个体发育：在这个独特的核心祖先中，干细胞的表征将有助于通过再生医学中的应用来回答基本的生物学问题。