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

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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