A human pluripotent stem cells-based platform to model physiological and diseased HSC development

Although hematopoietic stem cell (HSC) transplantation is routinely used to treat cancers and blood disorders, the persistent challenge of finding immunologically matched donors as well as engraftment failure or delayed reconstitution remain significant hurdles to HSC-based therapies. The objective of our studies is to define what regulates the emergence of HSCs during embryonic development. For this, we exploit the potential of human pluripotent stem cells (hPSC), that faithfully recapitulates early developmental events. Beside their fundamental importance for the improvement of our knowledge of basic biology of stemness, the insights generated from these studies will have clinical implications, such as the in vitro generation of HSCs and other blood cells for a wide array of regenerative medicine applications. In particular, we focus our attention on how mesodermal cells differentiate into hemogenic endothelial cells, the specialized endothelial cells that represent the progenitors of HSCs; how hemogenic endothelial cells transition into blood cells, with different degree of stemness; how HSCs maintain their identity. Our unique cellular and molecular tools, combined with our expertise in hematopoietic development and stem cell biology sets us in an ideal position to understand how we can generate and grow blood cells in a lab.