HOMEOBOX GENE EXPRESSED IN HEMATOPOIETIC STEM CELLS

造血干细胞中表达的同源盒基因

• 批准号: 2710353
• 负责人: BERNARD G FORGET
• 金额: $ 3.11万
• 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: 1999-06-30 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/2710353
• 关键词: cell differentiation; developmental genetics; gene expression; hematopoiesis; hematopoietic stem cells; homeobox genes; laboratory mouse; cell differentiation; developmental genetics; gene expression; hematopoiesis; hematopoietic stem cells; homeobox genes; laboratory mouse

Hematopoietic pluripotent or long-term reconstituting stem/progenitor cells represent a very small fraction of cells in the bone marrow which have the capacity for both self-renewal and differentiation along multiple pathways ultimately giving rise to all of the cellular elements of peripheral blood. Much remains to be understood about these cells and the patterns of gene expression that characterize them. In preliminary experiments, we have isolated a number of gene products (mRNAs/cDNAs) that are preferentially expressed in highly purified/enriched preparations of murine hematopoietic stem cells. One of these cDNAs derives from a homeobox gene that has been previously shown to have a tissue-restricted pattern of expression during murine development and mutations of which have been shown to be associated with (and are presumably responsible for) developmental disorders in humans. We now propose to directly study the function of this homeobox gene in the regulation of hematopoiesis by carrying out a number of studies in the laboratories of INSERM Unit 362 (W. Vainchenker, Director) at the Institut Gustave Roussy in Villejuif, France, where a number of different functional assays of hematopoietic stem cell proliferation and differentiation are available, as well as retroviral-based gene transfer techniques for transduction of hematopoietic stem/progenitor cells. The proposed research should provide a synergistic interaction between the laboratories of the applicant and the host institution, resulting in long-term collaborations and research productivity.

造血多能或长期重建茎/祖先 细胞代表骨髓中的一小部分细胞 具有自我更新和差异化的能力 多个途径最终会引起所有细胞元素 外周血。 关于这些细胞还有很多要理解的 以及它们表征它们的基因表达的模式。 在 初步实验，我们已经隔离了许多基因产物 （mRNA/cDNA）优先表达在高度 鼠造血干细胞的纯化/富集制剂。 一 这些cDNA衍生出以前曾经是的同源基因 显示在鼠期间具有组织限制的表达模式 已证明其发展和突变与 （可能是负责）人类的发育障碍。 现在，我们建议直接研究该同源基因在 通过在 Inserm 362的实验室（W. Vainchenker，董事） 在法国维勒利夫（Villejuif）的Gustave Roussy Institut 造血干细胞增殖的不同功能测定和 可用分化以及基于逆转录病毒的基因转移 造血干/祖细胞转导的技术。 这 拟议的研究应提供协同的相互作用 申请人和房东机构的实验室，导致 长期合作和研究生产力。