Budget Amount *help |
¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2012: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2011: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
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Research Abstract |
During mouse development, definitive hematopoiesis is first detected in the aorta-gonad-mesonephros (AGM) region at around embryonic day 10.5 (E10.5), which exhibits intra-aortic cell clusters (IACCs). These clusters are known to contain hematopoietic stem cells (HSCs). It is unclear how the cells in such clusters maintain their HSC phenotype. We found that a transcription factor, Sox17, and other F-group (SoxF) proteins, Sox7 and Sox18, were expressed in E10.5 IACCs. Overexpression of any of these SoxF proteins in IACCs led to consistent formation of cell clusters in vitro during several passages of cocultures with stromal cells. Sox17-transduced cells retained a long-term bone marrow reconstitution activity in vivo. Shutdown of exogenously introduced Sox17 gene expression resulted in immediate hematopoietic differentiation. These results indicate that SoxF proteins, especially Sox17, contribute to the maintenance of cell clusters containing HSCs in the midgestation AGM region.
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