高原低氧适应相关因子EPAS1是国内外研究的热点。目前认为，其表达在低氧环境下可反应性升高，并诱导EPO上升，进而促进红细胞生成。然而，本项目前期研究发现急进高原人群红细胞水平持续升高，而EPO浓度却先升高后降低至平原水平，提示存在非EPO途径调控红细胞生成。另有研究认为肿瘤细胞中EPAS1可激活Wnt/β-catenin信号通路，由此推测低氧条件下EPAS1可通过经典Wnt/β-catenin 信号通路促进造血干细胞的增殖与分化，进而影响红细胞生成。因此本项目拟进一步研究EPAS1、EPO和红细胞生成的相互关系，并分析低氧环境对HSC增殖及向红系祖细胞分化的影响；在阻断EPO通路的基础上，深入探索低氧环境下EPAS1经Wnt/β-catenin信号通路调控红细胞生成的作用机制。最终阐明EPAS1在高原低氧习服中的调控作用及新机制，为防治高原反应和红细胞增多症等疾病提供新的理论和实验依据。

The study of adaptation related factor EPAS1 to high altitude hypoxia has always been a hot topic.The expression of EPAS1 increased responsiveness under hypoxic environment, and induced the increase of EPO, thus promoting erythropoiesis, now. However, this project found that the erythrocyte level in the population rapidly entering the plateau continued to rise, while EPO concentration increased first and then decreased to the plain level, suggesting that there was a non-EPO pathway to regulate erythrocyte production. Some studies have suggested that EPAS1 can activate the Wnt/β-catenin signaling pathway in tumor cells. It is inferred that EPAS1 can promote the proliferation and differentiation of hematopoietic stem cells through classical Wnt/β-catenin signaling pathway under hypoxia, and then affect the formation of red blood cells. Therefore, this project intends to further study the relationship between EPAS1, EPO and erythropoiesis, and the effect of hypoxic environment on HSC proliferation and erythropoietic progenitor cell differentiation. On the basis of blocking EPO pathway, the mechanism of EPAS1 regulating erythropoiesis through non-EPO pathway under hypoxic environment is explored. This study may elucidate the regulatory role and mechanism of EPAS1 in altitude hypoxia acclimatization, and provide a new theoretical and experimental basis for the prevention and treatment of altitude reaction and erythrocytosis.