HEMATOPOIETIC PRECURSORS

描述(改编自申请人的摘要)：单个单元格， 多潜能造血干细胞(PHSC)，能够 重新填充所有的造血系，包括那些 免疫系统。这些干细胞存在于整个生命和 老鼠，那些从老年人身上分离出来的老鼠似乎有一种 作为祖先的能力不减，因此，在 至少，部分免除了对 大多数细胞。这项提议的目的是隔离和 确定这些干细胞的特征，并了解细胞和 支配它们分化的分子事件。一种理解 这些细胞对开发新的骨策略至关重要 骨髓移植和基因治疗。的第一个具体目标 这项建议是：研制BU/CY SCLD人-鼠嵌合体 系统作为人PHSC的检测方法，并用该方法鉴定 并对这些属性进行表征，这些属性将允许 分离高度浓缩的人类干细胞群体。这个 第二个具体目标是利用这些丰富的种群来检查 导致这一事件的事件以及参与其中的机制(S) 世代世系限制。调查人员将检查 IL-1对体内嵌合小鼠治疗的影响 IL-3、IL-4、IL-6、IL-7以及GM-、G-和M-CSF、SC-CF、LIF。 这些工作者将决定与世隔绝的人类的发展命运 多潜能造血细胞可通过暴露于 这些生长因子在体内或体外。巴施博士和科克斯希望 确定实施世系限制的时间 成熟的髓系祖细胞，并确定它们是否 与细胞因子反应性或受体的改变有关 表情。第三个具体目标是确定何时 髓系和淋巴系之间发生分离，并 确定T-和B-是否有不同的前兆 血统。调查人员希望能够确定 CD5+B细胞亚群可从骨髓PHSC和 它的发展需要哪些条件。

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.