从分子和细胞水平更好的了解血小板生成过程，将有助于解决临床基础研究中“如何获得大量治疗性的血小板”等重要问题。TPO-MPL途径为血小板生成的主要途径，并且在造血干细胞维持及再生、骨髓增生性疾病、骨髓衰竭等生理及病理过程也起重要作用。因此靶向TPO-MPL途径，聚焦于“有哪些因子调控造血干细胞向血小板系分化？依不依赖TPO-MPL途径？”的科学问题，本项目拟利用前期确立的TPO-MPL途径缺陷的、血小板可视化斑马鱼模型作为活体筛选工具，在活体动物中筛选TPO-MPL通路的调节子：进行基于化学诱变的抑制子和增强子的遗传学筛选，以及通路调节剂等小分子化合物的药物筛选，以发现新的血小板生成的新调控子，调控途径，甚至是候选的促血小板药物，并通过细胞学、遗传学、生化分子等方法研究其调控机制。研究结果将有可能绘制出血小生成的分子调控网络，并对理解相应的血液病发生机理奠定基础。

To obtain enough platelets for clinical usage, it is important to understand the molecular and cellular basis of thrombocytopoiesis. TPO-MPL pathway is the main path for generating thrombocytes, and it is also involved in hematopoiesis and hematological processes, including hematopoietic stem cell maintenance and regeneration, myeloid neoplasm syndromes, bone marrow failure and etc. Hence, targeting TPO-MPL pathway, we focus on finding factors regulating thrombocyte differentiation and unveil their regulatory mechanism, especially to find TPO-MPL independent pathway for thrombocytopoiesis. We plan to utilize the visualized model of TPO-MPL deficient zebrafish, to in-vivo screen genetic and chemical modifiers for TPO-MPL pathway. Through the screening and the characterization with cellular and molecular approaches, our aim is to find novel regulatory factors and new pathway for thrombocytopoiesis, even to find some potential drug candidates for promoting thrombocyte expansion. The research will help for understanding the molecular regulatory network for thromboctopoiesis and for unveiling the mechanism of related hematological disorders.