Characterisation of novel regulators of the haemopoeitic system.

所有循环中的血细胞(包括红细胞和白细胞)都是从成人骨髓中发现的一种称为造血干细胞(HSC)的单一细胞类型发展而来的。正常情况下，HSC会逐渐被限制为只成为一种细胞类型，一旦它们沿着该途径开始，就不能再产生另一种途径的细胞(例如，一旦HSC开始发育成红细胞，它们通常不能改变方向成为白细胞)。然而，有几个成熟细胞的例子改变了途径。我们已经使用了其中之一，小鼠的J2E红细胞转化为巨噬细胞，来识别参与这一过程的基因。我们发现的两个基因，HLS5和HLS7，在谱系决定和正常血液发育以及血癌的形成方面具有潜在的重要作用。该项目旨在研究这些基因在血液发育中所起的作用。到目前为止，我们的大部分工作都集中在HLS7上。人类等同于HLS7的基因是由一个独立于我们的美国组织发现的，它是一种导致一种血癌的基因。我们已经证明，HLS7对正常的血液发育有显著的影响，这些结果清楚地表明了该基因的重要性。通过我们对HLS7作用机制的研究，我们发现了另一个基因M44，它可能在HLS7的调控中起重要作用，并计划研究其功能。最后，HLS5与一组被称为转录因子的分子有相似之处，后者被认为是调节血液发育的关键因素。显然，对该基因的分析将进一步加深我们在这一领域的知识。

All of the circulating blood cells (including red cells and white cells) develop from a single cell type, called the haemopoietic stem cell (HSC), found in the adult bone marrow. Normally, HSCs are gradually restricted to become only one cell type and once they have started down that pathway can no longer generate cells of another pathway (e.g. once HSC begin to develop into red blood cells, they cannot normally change their direction to become white cells). There are a few examples of mature cells, however, that have changed pathways. We have use one of these, the mouse J2E red cell changing into macrophages, to identify the genes involved in this process. Two of the genes we found, HLS5 and HLS7, are potentially important in lineage determination and normal blood development as well as the formation of blood cancers. This project aims to investigate the roles these genes play in blood development. Much of our work to date has focused on HLS7. The human equivalent of HLS7 was found by an American group independently of us as a gene which causes one type of blood cancer. We have shown HLS7 has dramatic effects on normal blood development and, together, these results clearly show the importance of this gene. Through our studies on how HLS7 works, we have identified another gene, M44, which may be important in regulation of HLS7 and also plan to investigate is function. Finally, HLS5 has similarities to a group of molecules called transcription factors which are known to be key regulators blood development. Clearly, analysis of this gene will further our knowledge in this field.