The developmental hierarchy of haemopoietic lineage relationships

血细胞都是一种非常罕见的干细胞的后代，这种干细胞被认为存在于骨髓中。干细胞在个体的整个生命周期中维持自身，并产生血液中所需的数十亿种更成熟的细胞类型。然而，未成熟细胞从干细胞到最终成熟的功能血细胞(如淋巴细胞)的过程和阶段仍然存在争议。本研究旨在确定不同血细胞子代之间的相互关系，从而提供该系统的谱系图。为了做到这一点，我们将分离发育路径上不同阶段的前体细胞，并确定它们产生正常范围后代的能力。然后，我们将使用一些转基因小鼠品系来评估这一过程中涉及的基因。这些研究将有助于为开发一些干细胞疗法的尝试提供基本的科学基础，这些干细胞疗法旨在促进或指导白血病和免疫缺陷的骨髓移植等程序中的干细胞生产。此外，一些特征性的人类血液恶性肿瘤似乎已经沿着异常的途径发展，这表明不适当的谱系指定可能是癌症的一个因素。

The blood cells are all the progeny of a very rare stem cell, that is thought to reside in the bone marrow. The stem cell maintains itself throughout the life span of the individual as well as generating the billions of more mature cell types required in the blood. However the processes and stages that immature cells pass through from the stem cell to ultimately a mature functional blood cell such as a lymphocyte remain disputed. This study aims to determine to relationship of the various blood cell progeny with each other and thus to provide a lineage map of the system. To do this we will isolate precursors at various stages along the developmental pathways and determine their capabilities to produce the normal range of progeny. We will then use a number of genetically altered mouse strains to assess the genes involved in this process. These studies will help provide an underlying scientific basis to the attempts to development a number of stem cell therapies that are aimed at boosting or directing stem cell production in procedures such as bone marrow transplantation for leukemia and immune deficiency. In addition a number of characterized human blood malignancies seem to have developed along aberrant pathways indicating that inappropriate lineage specification may be a factor in cancer.