HOMEOBOX GENE EXPRESSED IN HEMATOPOIETIC STEM CELLS

造血多能或长期重建干/祖细胞 细胞代表骨髓中非常小的一部分细胞， 具有自我更新和分化的能力，沿着 多种途径最终导致所有的细胞成分 的外周血。 关于这些细胞还有很多东西有待了解 以及它们的基因表达模式。 在 初步实验，我们已经分离出一些基因产物 （mRNAs/cDNAs）优先在高表达的细胞中表达。 纯化/富集的鼠造血干细胞制剂。 一 这些cDNA来自一个同源框基因， 显示在小鼠中具有组织限制性表达模式 其发展和突变已被证明与 (and可能是造成人类发育障碍的原因。 我们现在建议直接研究这个同源异型盒基因的功能， 造血的调节，进行了一些研究， 362号机组的实验室（W。Vainchenker，导演） 法国维勒瑞夫的古斯塔夫·阿格西研究所， 造血干细胞增殖的不同功能测定和 分化以及基于逆转录病毒的基因转移 造血干/祖细胞转导技术。 的 拟议的研究应提供一个协同作用之间的相互作用， 申请人和东道机构的实验室， 长期合作和研究生产力。

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.