Control of blood cell emergence by YAP and environmental cues

成人一生中所有血细胞的生成都是由血液干细胞维持的。在临床上，移植这些血液干细胞可以成功地恢复在白血病或多发性硬化症等疾病中受损的完全功能的血液系统。在临床上使用造血干细胞移植的一个主要限制是移植受体配型供体的有限性。在体外产生这些用于临床目的的血液干细胞的可能性将大大促进这种治疗方法的使用。多能干细胞可以在体外有效地分化成所有的血液祖细胞，但研究人员仍在努力制造血液干细胞。利用多能干细胞作为体外模型系统生成血细胞，我们建议研究由培养条件创造的微环境如何影响不同类型血细胞的生成。我们将研究控制血细胞生成以响应微环境信号的分子机制。了解这一点将使我们最终能够精确地控制和操纵生物物理特性，以设计人造壁龛，以产生可用于临床的血液干细胞。

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.