血栓栓塞是慢性骨髓增殖性肿瘤（MPN）患者致残和致死主要原因之一。近年研究发现MPN患者具有JAK2/ V617F基因突变所导致的造血干细胞(HSCs)分化异常，临床研究证实该突变还是MPN患者血栓形成的高危因素。HSCs可以向血管内皮细胞分化，促进血管内皮修复和血管重建。而内皮细胞功能是否完善是血管血栓形成和血管修复的重要因素。本研究将在前期研究的基础上，通过小鼠MPN动物模型以及临床患者，从体内外研究JAK2/V617F基因突变对HSCs向内皮细胞分化和JAK/STAT信号通路的影响，研究由JAK2/V617F阳性HSCs分化而来的内皮细胞功能是否存在缺陷，并是否因此影响损伤的血管内皮修复，从而阐明CMPN患者是否存在由于该基因突变所导致的血管内皮修复障碍机制，从HSCs分化缺陷这一方面揭示MPN患者血栓发生机理，为该类患者血栓并发症的治疗提供新的思路和理论依据。

Thrombosis is one of the main causes of morbidity and mortality in myeloproliferative neoplasms (MPN) patients. It has been reported that JAK2V617F mutation plays a key role in abnormal differentiation of hematopoietic stem cells (HSCs), as well as in the consequent formation of MPN. Clinical researches also demonstrated that JAK2V617F mutation is a high risk factor for the formation of thrombosis in MPN cases. HSCs can differentiate into vascular endothelial cells (ECs), which then participate in both vascular repair and re-endothelialization of damaged blood vessels. And the fact that whether ECs function well or not is a major factor for vascular endothelium repair or thrombosis. Based on our previous work, in the present study, we used both mouse MPN model and clinical patients to investigate the in vitro and in vivo influence of JAK2V617F mutation on the differentiation of HSCs into ECs, whether the function of ECs differentiated from JAK2V617F-postive HSCs has any defects, and whether these defects influence the repair of injured ECs. We hope this study would clarify if the JAK2V617F mutation in CMPN patients can lead to the dysfunction of vascular endothelial repair, reveal the mechanisms involved in the formation of thrombosis in CMPN patients from the aspect of defective differentiation of HSCs, and provide novel ideas and theoretical basis for antithrombotic therapy in MPN patients.