Developmental origins and niches of the haematopoietic system

从生物学和治疗的角度来看，造血干细胞是一种重要的细胞。它们负责所有血细胞的终身生产。我们的工作重点是造血干细胞在胚胎中最初产生的第一个起源。我们的目标是更好地了解参与HSC生成、功能和维持的分子和机制。转录因子Runx1被证明在胚胎HSC的产生中起关键作用。在人类中，在大约25%的急性白血病中发现RUNX1的突变和易位，这表明RUNX1对于维持正常的造血功能也很重要。在我们的研究中，我们将通过鉴定Runx1调节的基因和途径，以及鉴定调节Runx1表达的途径，来研究Runx1如何在胚胎的第一批造血干细胞中发挥其关键作用。这些研究有望增加我们对造血干细胞生物学的认识，并有助于更好地理解白血病的发生，最终开发新的治疗方法。

Hematopoietic stem cells (HSCs) are important cells from a biological and therapeutic perspective. They are responsible for the life-long production of all blood cells. Our work focuses on the first origins of HSCs during their initial generation in the embryo. We aim to obtain a better understanding of the molecules and mechanisms that are involved in HSC generation, function and maintenance. The transcription factor Runx1 was shown to play a critical role in HSC generation in the embryo. In humans, mutations and translocations of RUNX1 are found in approximately 25% of acute leukaemias, indicating the importance of RUNX1 also for the maintenance of normal haematopoiesis. In our studies we will examine how Runx1 exerts its crucial role in the first HSCs of the embryo, by identification of the genes and pathways regulated by Runx1, and by identification of the pathways that regulate Runx1 expression. These studies are expected to increase our insight into the biology of HSCs, and can contribute to a better understanding of leukaemogenesis and ultimately the development of new therapies.