REGULATION OF THE HUMAN CD34 STEM CELL GENE

人类 CD34 干细胞基因的调控

• 批准号: 6828346
• 负责人: DANIEL G TENEN
• 金额: $ 39.47万
• 依托单位: BETH ISRAEL DEACONESS MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 1994
• 资助国家: 美国
• 起止时间: 1994-09-30 至 2007-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6828346
• 关键词: REGULATION; HUMAN; CD34; STEM; CELL

EXCEED THE SPACE PROVIDED. The human CD34 antigen is expressed specifically on human hematopoietic stem cells and not on mature blood cells, and CD34+ cells can reconstitute normal hematopoiesis of all cell lineages. CD34 is still the best defined human stem cell marker and is therefore a model for stem cell gene expression. Previous studies have defined some of the promoter elements for human and murine CD34, but the regulation of this and other stem cell genes is still very poorly understood, The distal elements necessary for human CD34 expression in vivo were recently isolated. The goal of this project is to continue to define and analyze the control elements of CD34, and to characterize those elements of the CD34 gene which can direct stem ceil expression of heterologous genes. The characterization of these elements could lead to the development of new vectors for gene therapy, as well as new understanding of the factors regulating genes in stem cells. Therefore, the specific aims are to characterize and study the regulatory elements of CD34 in the following steps: 1. To further characterize the important control elements regulating human CD34 gene expression in stem cells. 2. To characterize DNA binding proteins which regulate these elements. 1 To use CD34 regulatory elements expressing Cre recombinase and the tetracycline transactivator to enable tissue specific, regulatable expression of heterologous genes in the stem cell compartment. PERFORMANCE SITE ========================================Section End===========================================

超出所提供的空间。 人CD34抗原特异性表达于人造血干细胞而非成熟血细胞，CD34+细胞可重建所有细胞谱系的正常造血。CD34仍然是最好定义的人类干细胞标志物，因此是干细胞基因表达的模型。以前的研究已经确定了人和鼠CD 34的一些启动子元件，但对该基因和其他干细胞基因的调控仍然知之甚少。最近分离出了人CD 34体内表达所需的远端元件。本项目的目标是继续定义和分析CD34的控制元件，并表征那些可以指导异源基因干细胞表达的CD34基因元件。这些元素的特性可能导致新的基因治疗载体的开发，以及对干细胞基因调控因子的新理解。 因此，本论文的具体目标是通过以下步骤对CD34的调控元件进行表征和研究：1.进一步表征调节干细胞中人CD34基因表达的重要控制元件。2.表征调控这些元件的DNA结合蛋白。1使用表达Cre重组酶和四环素反式激活因子的CD34调控元件，使异源基因在干细胞区室中的组织特异性、可调控表达成为可能。性能现场=