中文摘要
造血干细胞是所有血液细胞的祖细胞,造血干细胞的发育分化对于形成有功能的效应细胞有着至关重要的作用。我们通过表达谱芯片分析了造血干细胞和下游分化的多能造血祖细胞 (MPP) 的差异表达基因。筛选到了在造血干细胞中特异高表达的功能未定义的B630005N14RIK基因。我们发现B630005N14RIK基因敲除小鼠的造血干细胞数量异常增多,而下游分化的淋巴细胞和髓系细胞数量明显减少,说明B630005N14RIK基因缺失导致造血障碍。通过酵母双杂交实验,我们筛选到了与B630005N14RIK基因相互作用的PBAF复合物的组分Brd7蛋白,并证明了它们在造血干细胞中的相互作用。本课题将研究B630005N14RIK蛋白与Brd7蛋白协同调控PBAF复合物的作用机制,阐明B630005N14RIK蛋白调控造血干细胞发育分化的分子机制。
英文摘要
Hematopoietic stem cells are progenitor cells for all the cells in hematopoietic system. The development and differentiation of HSCs are essential for the generation of effector cells. We analyzed the differential gens between HSCs and MPPs by gene microarray assy, and found that B630005N14RIK gene is highly expressed in HSCs, whose function is unknown. We noticed that knockout of B630005N14RIK caused abnormal increase of HSCs but reduction of lineage cells indicating that the deficiency of B630005N14RIK contributes to hematopoietic disorder. We further screened the interaction protein of B630005N14RIK by yeat-two hybrid assay and fished out a component of PBAF complex, Brd7 as its interation protein. We verified their interation in HSCs. We will study how B630005N14RIK regulate Brd7 to regulate PBAF complex, and illastrate the molecular mechanism of B630005N14RIK regulating the process of development and differentiation of HSCs.
