Mature blood cells are replenished daily throughout adult life. This continuous supply of cells is maintained by a tight control of the balance between self-renewal and differentiation of the haematopoietic stem cells (HSCs) residing at the apex of the haematopoietic hierarchy. Genetic or epigenetic alterations in the control of self-renewal and differentiation lead to haematological imbalance and ultimately to malignancies. The entire adult haematopoietic system depends on a finite number of HSCs, generated during embryonic life through a complex and still poorly understood developmental process. Haematopoietic cells originate from the mesoderm germ layer through a series of cell fate decisions. The first step toward haematopoietic commitment occurs with the formation of the haemangioblast, a mesodermal precursor giving rise to blood, smooth muscle and endothelium. Next, the activation of an endothelial-like programme in these mesodermal precursors leads to the formation of specialized progenitors termed haemogenic endothelium. Subsequently, haemogenic endothelial progenitors give rise to all blood cells, including HSCs, through an endothelial to haematopoietic transition during which the endothelial programme is actively shut-down.
Understanding how the haematopoietic programme is specified to produce HSCs during embryogenesis will provide critical insights into this basic developmental process leading to the generation of stem cells. Furthermore, understanding how HSCs are generated during embryonic life will enable us to produce these cells in vitro from differentiating embryonic stem cells for therapeutic applications. Finally, a comprehensive understanding of embryonic blood specification is essential to fully define the molecular steps leading to infant and childhood leukaemia for which genetic lesions are known to occur in utero.
Reader, Division of Developmental Biology and Medicine, University of Manchester, UK
Group Leader, CRUK Manchester Institute, University of Manchester, UK
Assistant Professor, Mount Sinai School of Medicine, New York, USA
Instructor, Mount Sinai School of Medicine, New York, USA
Postdoctoral training, National Jewish Centre, Denver, USA
PhD Laboratory of Molecular Genetics of Eucaryotes, Louis Pasteur University, Strasbourg, France