MOLECULAR BASIS OF MYELOPOIESIS

耶鲁大学医学院的合作研究人员共同致力于一个关于骨髓生成分子基础的项目。研究主题集中在鉴定和表征从多能造血干细胞到成熟、分化和功能性中性粒细胞的正常分化途径中至关重要的基因。这些主题结合在一起，努力提高我们对骨髓生成基因表达的分子解剖学以及调节髓系细胞分化、成熟和功能的特定途径的理解。该计划项目被组织成一个团队方法，由一个技术核心和一个管理核心支持四个研究项目的综合追求。个别项目涉及在原始造血干细胞中优先表达的同源盒基因(Pitx2)的作用和功能的表征；在早期造血中细胞表面抗原CD34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；与髓系白血病有关的干细胞分化障碍的分子基础的表征；以及成熟中性粒细胞激活时发生的基因表达变化的表征。该技术核心将为这些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，他们拥有广泛的基础研究专业知识，以解决一些重要的造血问题。

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.