| Project/Area Number |
16590939
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Hematology
|
|---|
| Research Institution | Osaka University |
|---|
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)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
NAKANO Toru Osaka University, Graduate School of Frontier Biosciences, Professor, 生命機能研究科, 教授 (00172370)
|
|---|
| Project Period (FY) |
2004 – 2005
|
| Project Status |
Completed (Fiscal Year 2005)
|
| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2005: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 2004: ¥1,800,000 (Direct Cost: ¥1,800,000)
|
|---|
| Keywords | Hematopoiesis / Differentiation / Embryonic stem cells / Transcription factor / Lineage switch / 血液 / 赤血球 / 巨核球 / マクロファージ / クロマチン構造 / 分子生物学 |
|---|
| 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.
|
