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The haemogenic endothelium: a key stage in the generation of the first blood cells

Previous and current research

The continuous generation of blood cells throughout life relies on the existence of hematopoietic stem cells (HSC) generated during embryogenesis. They have the ability to self-renew and to generate all types of blood cells. Any pathology affecting these cells could lead to development of serious diseases such as leukemia and anemia. That is why understanding how HSC and hematopoietic progenitors are produced during embryonic life is important.

The cellular origin of HSC has been the subject of an intense scientific debate during the last decade. However, in the last few years, several studies have allowed to single out one particular cell type as the source of HSC. It is a rare type of endothelial cells, the building block of blood vessels, endowed with hematopoietic potential. They form the hemogenic endothelium. The process of generation of blood cells from hemogenic endothelium is evolutionary conserved as it takes place in many different species including the mouse, the fish and ours.

Future projects and goals

Recently, the generation of the induced Pluripotent Stem Cells (iPSC) from fully differentiated cell type such as skin fibroblast, provided a major breakthrough for the field of regenerative medicine. Like Embryonic Stem Cells (ESC), iPSC have the capacity to generate any cell types of the body. Besides they offer a great opportunity to implement replacement therapy by bypassing the use of human embryos to generate ESC, therefore decreasing ethical concerns. However, important work has to be done to differentiate efficiently iPSC or ESC toward specific cell type including blood cell progenitors such as HSC.

Consequently, in order to better understand the development of the hematopoietic system, the focus of our research is to unravel the mechanisms underlying the generation of haemogenic endothelium and its subsequent commitment to hematopoiesis. Combining in vitro differentiation of mouse ESC with genomics, time-lapse microscopy, loss and gain of function in vitro and in vivo, we plan to identify and study the genes responsible for the generation of the first blood progenitors during embryonic life. Our aim is to gain a better understanding of the cell fate decisions leading to the production of the first hematopoietic cells and to use this knowledge to improve methods of blood cells generation from ESC or iPSC.