| Project/Area Number |
17590995
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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 |
SAKAI Eiko OSAKA UNIVERSITY, GRADUATE SCHOOL OF FRONTIER BIOSCIENCES, SPECIALLY APPOINTED ASSISTANT, 生命機能研究科, 特任助手 (60359859)
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| Co-Investigator(Kenkyū-buntansha) |
NAKANO Toru OSAKA UNIVERSITY, GRADUATE SCHOOL OF FRONTIER BIOSCIENCES, PROFESSPR, 生命機能研究科, 教授 (00172370)
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| Project Period (FY) |
2005 – 2006
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| Project Status |
Completed (Fiscal Year 2006)
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| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2006: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2005: ¥2,200,000 (Direct Cost: ¥2,200,000)
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| Keywords | HEMATOPOIESIS / UNDIFFERENTIATION / TRANSCRIPTION FACTOR / runx1 / hoxb4 / OP9 |
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| Research Abstract |
Definitive hematopoiesis originates from the hemogenic endothelial cells during mouse embryogenesis. Runxl is essential for both the development of definitive hematopoiesis and the homeostasis of adult hematopoiesis. We carried out the analyses using combined in vitro hematopoietic differentiation from ES cells and conditional gene expression. Expression of runxl at the stage of multipotential progenitors promoted maturation of erythroid and megakaryocytic lineages. Meanwhile, pulse expression during differentiation from hemogenic to hematopoietic cells caused immature hematopoietic cell expansion in the population that was newly emerged from endothelial cells. During this process, several endothelial-cell-specific genes were down-regulated and Flt3 ligand was up-regulated. In addition, the normal expression pattern of flt3 ligand in the aorta-gonads mesonephros region was disrupted in the runxl% embryo. Overall, the single-experiment system adopted in this study provides evidence that runxl plays dual roles within an unexpectedly narrow window to accomplish precise regulation of differentiation and proliferation at early definitive hematopoiesis.
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