| Project/Area Number |
07670832
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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 Professor, 医学部, 教授 (60003480)
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| Co-Investigator(Kenkyū-buntansha) |
TOKI Tsutom Hirosaki University, School of Medicine Instructor, 医学部, 助手 (50195731)
ITO Etsuro Hirosaki University, University Hospital Assistant Professor, 医学部附属病院, 講師 (20168339)
北澤 淳一 弘前大学, 医学部・附属病院, 助手
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| Project Period (FY) |
1995 – 1996
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| Project Status |
Completed (Fiscal Year 1996)
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| Budget Amount *help |
¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 1996: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1995: ¥1,400,000 (Direct Cost: ¥1,400,000)
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| Keywords | Aplastic anemia / GATA-1 transcription factor / NF-E2 transcription factor |
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| Research Abstract |
In order to understand the pathology of aplastic anemia, we have studied the expression of the transcription factors which may play important roles in normal hematopoiesis reverse transcriptase mediated polymerase chain reaction (RT-PCR). In this study, we analyzed the expression patterns of GATA-1, GATA-2, NF-E2, Nrf1, Nrf2 and Ets-1 mRNA as well as erythroid specific genes such as globins and erythropoietin receptor (EpoR) in purified early hematopoietic progenitor cells (HPCs) induced to unilineage erythroid or megakaryocytic differentiation in a liquid culture system. The results showed that the profile of these transcription factors expression megakaryocytic cells is similar but distinct from erythroid lineage. The major differences betweenthe two lineages were the expression pattern of GATA-2. The high level of GATA-2 expression is induced and maintained as megakaryocytic maturation progresses, whereas expression of this factor decline as erythroid terminal differentiation progresses. GATA-1, Nrf1 and Nrf2 showed very similar expression profile in both lineages. These observations were confirmed by using chronic myelogenous leukemia (CML) blasts which can be induced into both lineages in our liquid culture system. NF-E2 is a heterodimer composed of a lineage-specific subunit p45 and a ubiquitous subunit p18 which belongs to small Maf family. We cloned the human cDNAs for MafK and MafG for the first time. Surprisingly mafK and mafG mRNA increased markedly during erythroid and megakaryocytic differentiation as well as p45 NF-E2. Moreover, erythroid-specific genes such as globins and EpoR were upregulated during the differentiation toward the both lineages indicating the both differentiation pathways are very closed. In present study, we clarify the normal expression pattern of lineage-specific transcription factors and these results will be very useful of understanding the pathology of aplastic anemia.
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