| Project/Area Number |
09670777
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Pediatrics
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| Research Institution | HIROSAKI UNIVERSITY |
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Principal Investigator |
YOKOYAMA Masaru Hirosaki University, School of Medicine, Pediatrics, Professor, 医学部, 教授 (60003480)
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| Co-Investigator(Kenkyū-buntansha) |
TOKI Tsutomu Hirosaki University, School of Medicine, Pediatrics, Instructor, 医学部, 助手 (50195731)
ITO Etsuro Hirosaki University Hospital, Pediatrics, Assistant Professor, 医学部・付属病院, 講師 (20168339)
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| Project Period (FY) |
1997 – 1999
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| Project Status |
Completed (Fiscal Year 1999)
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| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 1999: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 1998: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 1997: ¥2,400,000 (Direct Cost: ¥2,400,000)
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| Keywords | GATA transcription factors / NF-E2 transcription factors / CATA転写因子 / 赤血球 / 造血幹細胞 / 転写因子 / NF-E2 / GATA-1 |
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| Research Abstract |
Lineage specific transcription factors, GATA-1 and NF-E2 are essential for erythropoiesis and megakaryocytopoiesis. In order to shed light on the erythroid development of human hematopoietic stem cells, we performed cDNA cloning of novel NF-E2 related transcription factors, Nrf3, BACH1 and BACH2.
Although normal megakaryocytic development has been shown to require the presence of a functional GATA-1 factor in vivo, the role of other members of the GATA binding factors during megakaryocytic differentiation is unclear. In this report, the expression of GATA-1 and GATA-2, and another GATA binding factor EVI-1 has been examined in enriched cord blood progenitors before and after culture in a well-characterized unilineage liquid culture system. In the culture containing only thrombopoietin, which show exclusive megakaryocytic differentiation, both GATA-1 and GATA-2 expression was increased and maintained at high levels. In contrast, GATA-2 expression declined in unilineage erythroid culture, although GATA-1 remained at a high level. Furthermore, the profile of EVI-1 expression in megakaryocytic and erythroid lineages was very similar to that of GATA-2. Because Ets binding sites associated with GATA binding sites are present in all regions that have been described as important for megakarycyte-specific expression, we also analyzed Ets-1 expression. Interestingly. Ets-1 was induced only in megakaryocytic lineage cells. Megakaryocytic and erythroid differentiation pathways are closely related to each other, and these two lineage cells share a number of lineage-specific transcription factors. However, the results showed that the profile of the expression of these transcription factors in megakaryocytic cells is distinct from that of erythroid lineage. The dynamic changes in the levels of GATA binding factors that occur during primary megakaryocytic differentiation suggest that the levels of these factors may influence the progression to specific hematopoietic pathways.
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