单核巨噬细胞系统是人类免疫防御的重要屏障，其分化稳态失调可引起急性髓系白血病和儿童川崎病等血液疾病。尽管成熟单核巨噬细胞的功能有较多报道，但其分化机制所知甚少。明确单核巨噬细胞分化稳态的转录调控机制是亟待解决的基础医学问题。我们发现Stat1可能是调控这一过程的关键转录因子（Blood 2014，Leukemia 2015）。尽管Stat1在抗感染和抑癌方面有诸多报道，由于研究工具的限制，它在单核巨噬细胞分化中的调控作用尚未揭示。本研究以斑马鱼转基因系、人成单核细胞系、及胚胎干细胞为工具，揭示单核巨噬细胞分化中Stat1对分化细胞的形态功能的调控作用，并通过研究Stat1与c-Jun、mTOR-C/ebpα等的交互作用，阐明其在稳态维持和分化中的分子机制。并筛选可模拟Stat1作用的化合物，分析儿童川崎病及急性髓系白血病临床样本中Stat1与病理进程的关联，为相关疾病的治疗提供新的策略。

The monocytes-macrophages system is the important barrier of human immunity defense. The disorder of its differentiation homoestasis leads to acute myeloid leukemia, children Kawasaki disease and other hematopoietic diseases. Although the function of mature monocytes-macrophages is frequently reported, the molecular mechanism of their differentiation remains largely unknown. The understanding of key transcriptional regulators in differentiation hemostasis of monocytes-macrophages is an urgent project of the basic medicine. Our previous study shows that Stat1 is the possible key transcriptional regulator in monocytes-macrophages differentiation (Blood 2014，Leukemia 2015). In spite of many reports in anti-infection and anti-tumor function of Stat1, its regulation function in monocytes-macrophages differentiation is unveiled. In this study, transgenic lines of monocytes-macrophages in zebrafish, in vitro human monoblastic cell lines and embryonic stem cells tools are employed to explore effects of Stat1 on the morphology and function of differentiating monocytes-macrophages. We then try to illustrate the molecular mechanism of Stat1 in the regulation of differentiation homoestasis of monocytes-macrophages by studying the interaction between Stat1 and c-Jun, mTOR-C/ebpα and so on. Furthermore, we will use high-throughput screening to identify the chemicals that simulate the Stat1 function, and plan to collect the clinic samples of children Kawasaki disease and acute myeloid leukemia to analyze the association between Stat1 and the pathological process. This study might provide a new therapy strategy to related hematopoietic diseases.