Developmental origins and niches of the haematopoietic system

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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.