GPS2参与炎症、肥胖、胰岛素耐受等生物学过程的调控，但至今未见其参与造血作用调控的报道。我们前期的研究发现：1）GPS2在造血干细胞中表达并在红系分化中上调；2）在K562和人脐带血CD34+细胞中敲低GPS2显著抑制红系分化；3）GPS2与红系调控转录因子GATA1相互作用并调节其活性。表明GPS2在红系发育中发挥了重要作用。本项目拟在前期工作的基础上，采用体外（K562和人脐带血CD34+细胞）、体内（异种移植和基因敲除小鼠）模型系统研究GPS2对造血干细胞分化特性的影响，并深入探讨其分子机制。主要研究内容包括：1）过表达或干涉GPS2对K562及脐带血CD34+细胞红系分化的影响；2）采用异种移植模型评价GSP2体内对造血干细胞谱系分化的影响；3）采用已构建的GPS2敲除小鼠研究GPS2对造血谱系的影响；4）以GPS2与GATA1相互作用为重点，探讨GPS2调控红系分化的分子机制。

GPS2 is a transcription co-factor involved in the regulation of inflammation, obesity, insulin resistance and some other biologic processes, but its function in hematopoiesis is still unclear. Previous studies in our lab showed that: 1) GPS2 was expressed in hematopoietic stem cells, and increased expression of GPS2 was observed during erythroid differentiation. 2) knock down of GPS2 could inhibit the erythroid differentiation of human erythroleukemic cell line K562 and human cord blood CD34+ cells. 3) GPS2 could interact with erythroid transcriptional factor GATA1, and regulate its activity. Accordingly, we presumed that GPS2 could play a critical role in erythropoiesis. Therefore, We intend to do a systematic research on the effects and molecular mechanisms of GSP2 in erythropoiesis: 1) the regulation of GPS2 in erythroid differentiation of K562 cells and human cord blood CD34+ cells in vitro, 2) the regulation of GPS2 in erythroid differentiation of human cord blood CD34+ cells transplanted into NOD/SCID/IL2Rγnull mice, 3) the hematopoietic lineage commitment in GPS2 knockout mice, 4) the molecular mechanisms of GPS2 in the regulation of erythropoiesis. This study will reveal novel functions of GPS2 in erythropoieis as well as discover novel mechanisms in the regulation of erythroid differentiation.