MOLECULAR BASIS OF MYELOPOIESIS

骨髓细胞生成的分子基础

• 批准号: 6184708
• 负责人: BERNARD G FORGET
• 金额: $ 163.71万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-08-01 至 2004-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6184708
• 关键词: hematopoiesis; myeloid stem cell

Collaborating Investigators at Yale University School of Medicine have jointly devoted a Program Project on the molecular basis of myelopoiesis. The research themes focus on the identification and characterization of genes that are critical to the normal pathway of differentiation from the pluripotent hematopoietic stem cell, through intermediate progenitor and precursor cell stages, to mature differentiated and functional neutrophils. These themes coalesce in efforts to improve our understanding of the molecular anatomy of gene expression in myelopoiesis and the specific pathways that regulate the differentiation, maturation and function of myeloid cells. This Program Project is organized into a team approach for the integrated pursuit of four research projects supported by one technical core and one administrative core. The individual projects address the characterization of the role and function of a homeobox gene (Pitx2) that is preferentially expressed in primitive hematopoietic stem cells; characterization of transcription factors and genetic sequences required for the cell-type specific expression of the cell surface antigen CD34 in early hematopoiesis; characterization of the molecular basis for the block in stem cell differentiation that is associated with myeloid leukemia, and characterization of the changes in gene expression that occur with activation of mature neutrophils. The technical core will provide the following state- of-the-art services to the projects: protein purification, protein expression analysis and gene expression analysis. This Program Project application brings together investigators from four different departments of the institution, with a wide variety of basic research expertise to address a number of important questions in hematopoiesis.

耶鲁大学医学院的合作研究人员共同致力于骨髓生成分子基础的计划项目。研究主题集中在对多能造血干细胞分化的正常途径至关重要的基因的鉴定和表征，通过中间祖细胞和前体细胞阶段，成熟分化和功能性中性粒细胞。这些主题结合在一起，努力提高我们的理解的基因表达在骨髓细胞和特定的途径，调节分化，成熟和功能的髓样细胞的分子解剖。该计划项目被组织成一个团队的方法，由一个技术核心和一个行政核心支持的四个研究项目的综合追求。个别项目涉及优先在原始造血干细胞中表达的同源框基因（Pitx 2）的作用和功能的表征;早期造血中细胞表面抗原CD 34的细胞类型特异性表达所需的转录因子和遗传序列的表征;表征与髓性白血病相关的干细胞分化阻滞的分子基础，以及对成熟嗜中性粒细胞激活时发生的基因表达变化的表征。 技术核心将为项目提供以下最先进的服务：蛋白质纯化、蛋白质表达分析和基因表达分析。该计划项目申请汇集了来自该机构四个不同部门的研究人员，他们具有各种基础研究专业知识，以解决造血中的一些重要问题。