Control of blood cell emergence by YAP and environmental cues

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The generation of all blood cells throughout adult life is maintained by blood stem cells. In the clinic, upon transplantation these blood stem cells can successfully restore a fully functional blood system which is compromised in diseases such leukaemia or multi-sclerosis. One major limitation to the use of blood stem cell transplantation in the clinic is the restricted availability of compatible donor for graft recipients. The possibility to generate these blood stem cells in vitro for clinical purposes would significantly advance the use of this curative treatment. Pluripotent stem cells can be efficiently differentiated in vitro to form all blood progenitors but researchers are still struggling to generate blood stem cells.Using pluripotent stem cells as an in vitro model system to generate blood cells, we propose to investigate how the microenvironment created by the culture conditions may affect the generation of different types of blood cells. We will investigate the molecular mechanisms which control the generation of blood cells in response to signals from the microenvironment. Understanding this will allow us ultimately to precisely control and manipulate biophysical properties for the design of artificial niches to generate blood stem cells usable in the clinic.