Functional analysis of transcription factors on development and defferentiation of hematopoietic cells

我们从这个研究项目中确定了两件事。一个是DATA转录因子在嗜酸性粒细胞发育中的作用，另一个是MafB在巨噬细胞发育中的作用。1)GATA转录因子在嗜酸性粒细胞发育中的作用。在嗜酸性粒细胞中观察到高水平的GATA-1和gata表达，但它们在体外和体内嗜酸性粒细胞发育中的作用仍不确定。我们发现，在人原代髓系祖细胞中，GATA-1的强制表达完全将髓系细胞转变为嗜酸性细胞。GATA-1的表达专门促进嗜酸性粒细胞的发育和终末成熟。gata -1缺陷小鼠在胎儿肝脏中不能产生嗜酸性粒细胞祖细胞。另一方面，DATA-2在体外也显示出与GATA-1相当的指导能力，并且在体内有效地弥补了GATA-1在嗜酸性粒细胞发育方面的不足，表明GATA因子的适当积累对嗜酸性粒细胞的发育至关重要。综上所述，我们的研究结果确定了GATA因子在嗜酸性粒细胞发育中的重要和指导性作用。GATA-1和GATA-2可能成为治疗过敏性炎症的新分子靶点2)mab在巨噬细胞发育中的功能。为了研究可疑的MafB在造血中的功能，他们产生了MafB /GFP敲入零突变小鼠。在造血细胞中，GFP的表达在粒细胞、骨髓单核细胞和分化的巨噬细胞亚群中被特异性观察到，研究人员发现，巨噬细胞亚群的发育和正常功能需要MafB

We identified two things from this research projects. One is the function of DATA transcription factors in eosinophil development and the other is MafB function in Macrophage development1)The function of GATA transcription factors in eosinophil development. A high level of GATA-1 and GATA-expression has been observed in eosinophils, but their roles in eosinophil development remain uncertain both in vitro and in vivo. We showed that enforced expression of GATA-1 in human primary myeloid progenitor cells completely switches myeloid cell fate into eosinophils. Expression of GATA-1 exclusively promotes development and terminal maturation of eosinophils. GATA-1-deficient mice failed to develop eosinophil progenitors in the fetal-liver. On the other hand, DATA-2 also showed instructive capacity cumparable to GATA-1 in vitro and -efficiently compensated for GATA-1 deficiency in terms of eosinophil development in vivo, indicating that proper accumulation of GATA factors is critical for eosinophil development. Taken together, our findings establish essential and instructive roles of GATA factors in eosinophil development. GATA-1 and GATA-2 could be novel molecular targets for therapeutic approaches to allergic inflammation2)MafB function in Macrophage development. To investigate suspected MafB functions in hematopoiesis, the generates mafB/GFP knock-in null mutant mice. In hematopoietic cells, GFP expression was specifically observed in a subpopulation of granulocytes, myelomonocytes and differentiated macrophages, and eve identified that MafB was required for the development and normal function of a discrete subset of macrophages