巨核细胞分化成熟障碍是免疫性血小板减少症（ITP）等许多血小板疾病发生的主要原因，但其中的分子调控机制尚不明确。前期研究我们发现ITP患者巨核细胞粘附及骨架重排能力存在明显的缺陷，且巨核细胞中Hippo通路关键分子YAP1表达明显降低，因此我们提出假说Hippo通路可能参与ITP发病中巨核细胞的成熟产板过程，为深入探究Hippo通路调控巨核细胞成熟产板的机制，本课题将开展以下研究：1.利用ITP患者和正常人巨核细胞明确Hippo信号通路与巨核细胞成熟障碍的相关性；2.经体外细胞实验阐明Hippo信号通路通过YAP1调控巨核细胞的成熟以及产板的作用机理；3.利用小鼠ITP模型，进行Hippo通路调控干预ITP的转化研究。该研究将阐明Hippo通路通过YAP1及下游蛋白调控巨核细胞成熟以及产板的分子机制，为寻找预防诊断和干预巨核成熟障碍性疾病的新靶点的开发和应用提供实验基础。

Megakaryocyte differentiation and maturation dysfunction contributes to many platelet associate diseases such as immune thrombocytopenia (ITP). However, the underlying mechanisms remains uncertain. Our previously studies showed that there was a certain degree of deficiencies in megakaryocyte adhesion and cytoskeleton reorganization in the ITP patients. Further studies showed that the expression of YAP1, the key regulator of Hippo in the megakaryocytes from ITP patients was significantly decreased, thus we proposed an important regulatory role of the Hippo pathway in the maturation of megakaryocytes. In order to investigate its underlying mechanism, we will firstly use ITP patient and healthy volunteer megakaryocytes to clarify the correlation between Hippo signaling pathway and megakaryocyte maturation dysfunctions. Following in vitro experiments to demonstrate the regulation of Hippo signaling pathway on megakaryocyte maturation and platelet production via YAP1. Finally, using ITP mouse models to carry out the translational study of Hippo pathway regulation for ITP intervention. This study will shed light on the molecular mechanism of the Hippo pathway regulating megakaryocyte maturation and platelet production through YAP1 and downstream proteins, providing an experimental basis for the development and application of new targets for the prevention of diagnosis and intervention of megakaryocyte maturation related diseases.