REGULATION OF THE HUMAN CD34 STEM CELL GENE

超出所提供的空间。人CD34抗原在人造血干细胞上特异性表达，而不是在成熟血细胞上表达，CD34+细胞可以重建所有细胞系的正常造血。CD34仍然是最明确的人类干细胞标记物，因此是干细胞基因表达的模型。先前的研究已经确定了人类和小鼠CD34的一些启动子元件，但对这些和其他干细胞基因的调控仍然知之甚少。最近分离出了人类CD34在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CD34基因中那些可以指导异源基因在干细胞中的表达的元件。这些元素的表征可能导致基因治疗的新载体的发展，以及对干细胞中调节基因的因素的新认识。因此，具体目的是通过以下步骤对CD34的调控元件进行表征和研究：进一步表征在干细胞中调节人类CD34基因表达的重要控制元件。2. 描述调节这些元素的DNA结合蛋白。1 .利用表达Cre重组酶和四环素反激活因子的CD34调控元件，实现干细胞室中异源基因的组织特异性、可调控表达。网站性能 ======================================== 节结束 ===========================================

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===========================================