| Budget Amount *help |
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2011: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2010: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000)
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| Research Abstract |
1. Analysis of KS-13 signal. By database of KS-13, we identified Hmgn2, which gene expression is down-regulated during erythroid differentiation. Over-expression of Hmgn2 gene into leukemic cell lines resulted in suppression of erythroid differentiation in vitro(Kulkeaw et al., 2012).
2. Identification of novel molecules that regulate differentiation of hematopoietic stem cells. Fetal liver comprises hematopoietic cells, hepatoblasts and sinusoid endothelial cells. By Flow cytometry, we sorted out Dlk-1(+) hepatoblasts, which primarily expressed extra-cellular matrix such as fibronectin and vitronectin, in addition to hematopoietic cytokines, SCF and EPO(Sugiyama et al., 2011). We have submitted the paper about extra-cellular matrix(Sugiyama et al., in revision).
To further investigate the roles of hepatoblasts, we used the mutant mice lacking both hepatoblasts and hepatocytes. We sorted out CD45(+) c-Kit(+) Sca-1(+) hematopoietic stem cells from E19. 5 fetal liver of both mutants and wild type control and transplanted into irradiated recipient mice. Three to six months after transplantation, hematopoietic reconstitution was analyzed by flowcytometry. The chimerism of wild type control was achieved to over 5%, whereas that of mutants was less than 0. 5%. Using these samples, we performed micro-array analysis and identified several candidate genes that likely regulate differentiation of hematopoietic stem cells.
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