2005 Fiscal Year Final Research Report Summary
Hematopoietic lineage determination by transcription factors.
| Project/Area Number |
16590939
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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 |
Hematology
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| Research Institution | Osaka University |
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Principal Investigator |
KITAJIMA Kenji Osaka University, Graduate School of Medicine, Specially appointed Associate Professor, 医学系研究科, 特任助教授(常勤) (10346132)
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| Co-Investigator(Kenkyū-buntansha) |
NAKANO Toru Osaka University, Graduate School of Frontier Biosciences, Professor, 生命機能研究科, 教授 (00172370)
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| Project Period (FY) |
2004 – 2005
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| Keywords | Hematopoiesis / Differentiation / Embryonic stem cells / Transcription factor / Lineage switch |
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| Research Abstract |
GATA-2 is a zinc finger transcription factor essential for differentiation of immature hematopoietic cells. We analyzed the function of GATA-2 by a combined method of tetracycline-dependent conditional gene expression and in vitro hematopoietic differentiation from mouse embryonic stem (ES) cells using OP9 stroma cells (OP9 system). In the presence of macrophage colony-stimulating factor (M-CSF), the OP9 system induced macrophage differentiation. GATA-2 expression in this system inhibited macrophage differentiation and redirected the fate of hematopoietic differentiation to other hematopoietic lineages. GATA-2 expression commencing at day 5 or day 6 induced megakaryocytic or erythroid differentiation, respectively. Expression levels of PU.1,a hematopoietic transcription factor that interferes with GATA-2,appeared to play a critical role in differentiation to megakaryocytic or erythroid lineages. Transcription of PU.1 was affected by histone acetylation induced by binding of GATA-2 to the PU.1 promoter region. This study demonstrates that the function of GATA-2 is modified in a contextdependent manner by expression of PU.1, which in turn is regulated by GATA-2.
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Research Products
(10 results)
