HEMATOPOIETIC PRECURSORS

描述（改编自申请人的摘要）：单个细胞， 多能造血干细胞（PHSC），能够 恢复所有的造血谱系，包括那些 免疫系统 这些干细胞存在于整个生命过程中， 从老年人中分离出来的小鼠似乎具有 作为祖细胞的能力没有减弱，因此， 至少，部分免除对 大多数细胞 这项建议的目的是隔离和 表征这些干细胞，并了解细胞和 控制它们分化的分子事件。 的理解 对于开发新的骨骼策略至关重要 骨髓移植和基因治疗。 第一个具体目标 本研究拟：开发BU/CY SClD人-鼠嵌合体 系统作为人PHSC测定，并使用该测定来鉴定 这些细胞和表征这些属性，这将允许 分离高度富集的人干细胞群。 的 第二个具体目标是利用这些富集的群体来检查 导致冲突的事件及其所涉机制 血统限制的产生。 调查人员将检查 用IL-1体内处理嵌合小鼠的影响， IL-3、IL-4、IL-6和IL-7以及GM-、G-和M-CSF、SC-CF和LIF。 这些工人将决定是否孤立的发展命运 多能造血细胞可以通过暴露于 这些生长因子在体内或体外。 巴什博士和考克斯希望 确定血统限制的时间 骨髓祖细胞，因为他们成熟，并确定这些是 与细胞因子反应性或受体 表情 第三个具体目标是确定 髓系和淋巴系之间发生分离， 确定T-和B-是否存在单独的前体 血统 调查人员希望能够确定 人B细胞的CD 5+亚群可以从骨髓PHSC发育， 它的发展需要什么样的条件。

DESCRIPTION (Adapted from applicant's abstract): A single cell, the pluripotential hematopoietic stem cell (PHSC), is capable of repopulating all of the hematopoietic lineages including those of the immune system. These stem cells are present throughout life and in mice, those isolated from aged individuals appear to have an undiminished capacity to act as progenitors and are therefore, at least, partially exempt from the life-span restrictions imposed on most cells. The object of this proposal is to isolate and characterize these stem cells and to understand the cellular and molecular events which govern their differentiation. An understanding of these cells is crucial to developing new strategies for bone marrow transplantation and gene therapy. The first specific aim of this proposal is to: develop the BU/CY SClD human-mouse chimeric system as an assay for human PHSC and use this assay to identify these cells and characterize those properties which will permit the isolation of a highly enriched population of human stem cells. The second specific aim is to use these enriched populations to examine the events leading to, and the mechanism(s) involved in, the generation of lineage restriction. The investigators will examine the influence of treatment of the chimeric mice in vivo with IL-1, IL-3, IL-4, IL-6 and IL-7 as well as GM-, G- and M-CSF, SC-CF and LIF. These workers will determine if the developmental fate of isolated multipotential hematopoietic cells can be altered by exposure to these growth factors in vivo or in vitro. Dr. Basch and corkers hope to establish the timing of the lineage restrictions imposed on myeloid progenitors as they mature and determine if these are associated with alterations in cytokine responsiveness or receptor expression. The third specific aim is to establish when the separation between the myeloid and lymphoid lineages occurs and to determine if there are separate precursors for the T- and B- lineages. The investigators expect to be able to determine if the CD5+ subset of human B cells can develop from bone marrow PHSC and what conditions are required for its development.