Defining a Niche: How a Blood Stem Cell Niche Develops

定义利基：血液干细胞利基如何发展

• 批准号: 7111202
• 负责人: Teresa V Bowman
• 金额: $ 4.6万
• 依托单位: BOSTON CHILDREN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-08-01 至 2008-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7111202
• 关键词: Wnt gene /protein; animal breeding; biological signal transduction; biotechnology; bone marrow; bone morphogenetic proteins; cell differentiation; cell migration; cell proliferation; confocal scanning microscopy; developmental genetics; gene mutation; genetic screening; genetically modified animals; hematopoiesis; hematopoietic stem cells; kidney cell; molecular cloning; nonmammalian vertebrate embryology; postdoctoral investigator; stromal cells; vascular endothelium; zebrafish

DESCRIPTION (provided by applicant): Tight regulation of internal and external factors controlling blood cells is important in maintaining tissue homeostasis and preventing myeloproliferative disorders and leukemias. In particular, hematopoietic stem cells and their supportive microenvironment are at the root of hematopoietic tissue homeostasis. The mechanisms underlying the development and maintenance of the adult hematopoietic stem cell niche are largely unknown. Using the genetic model Danio rerio (zebrafish), I propose to identify and characterize genes important to the development and maintenance of the adult hematopoietic stem cell niche. I will use fluorescent time-lapse confocal microscopy to dynamically monitor the development of the niche in zebrafish. The information from this analysis will be the basis for a forward genetic screen to identify genes necessary for adult hematopoietic niche formation. Genes identified will include those required for the biological migration, expansion, and survival of adult hematopoietic cells within the niche. Additionally, the results from the proposed study can reveal potential pathways misregulated in disease states. Information gained in this screen will be useful in developing novel therapies for hematologic malignancies and immune deficiencies.

描述（由申请人提供）：控制血细胞的内部和外部因素的严格调节对于维持组织稳态和防止骨髓增生性疾病和白血病很重要。特别是，造血干细胞及其辅助微环境是造血组织稳态的根源。成人造血干细胞生态位开发和维持的基础机制在很大程度上是未知的。我建议使用遗传模型Danio Rerio（斑马鱼），建议识别和表征对成人造血干细胞壁se的发展和维持重要的基因。我将使用荧光延时共聚焦显微镜，以动态监测斑马鱼中生态市场的发展。该分析中的信息将是向前遗传筛选的基础，以识别成人造血生态裂阵列形成所需的基因。确定的基因将包括生物迁移，扩张和成年造血细胞内生存所需的基因。此外，拟议的研究的结果可能揭示了疾病状态中误导的潜在途径。在此屏幕上获得的信息将有助于开发用于血液系统恶性肿瘤和免疫缺陷的新型疗法。