The regulatory mechanisms of self-proliferation and differentiation in stem cells
| Project/Area Number |
10680693
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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 |
Developmental biology
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| Research Institution | Tottori University |
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Principal Investigator |
SHIRAYOSHI Yasuaki Tottori Univ., Dept.Med.Associate Professor, 医学部, 助教授 (90249946)
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| Co-Investigator(Kenkyū-buntansha) |
NAKATSUJI Norio Kyoto Univ., Dept.Med.Professor, 医学部, 教授 (80237312)
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| Project Period (FY) |
1998 – 2000
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| Project Status |
Completed (Fiscal Year 2000)
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| Budget Amount *help |
¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 2000: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1999: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 1998: ¥1,400,000 (Direct Cost: ¥1,400,000)
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| Keywords | Notch4 / Stem cells / Hematopoietic stem cells / Endothelial cells / Gene targeting / Notch / 造血幹細胞 / ジーンターゲッティング |
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| Research Abstract |
Members of Notch gene family encode transmembrane proteins that play roles in inhibition of differentiation among neighboring cells and mediate cell fate decisions of stem cells. The embryonic expression of mouse Notch4, a common integration site for MMTV in mammary tumors, is largely restricted to vascular endothelial cells. These results suggested that the Notch signaling pathway plays a critical role in vascular development.
In this study we attempted to produce the knockout mouse of Notch4 by gene targeting in order to investigate the role of the Notch4 gene in vascular development. Chimeric mice have been crossed to generate heterozygous knockout mice. Moreover, we also use the in vitro differentiation system of embryonic stem (ES) cells for hematopoietic and endothelial cells, and examine the effect of activated Notch4 on the differentiation of ES cells. The analysis of expression in several marker genes show that activated Notch4 inhibits the differentiation of ES cells at the very early stage as well as the branching point of hemangioblast cell lineage toward hematopoietic cells or endothelial cells. These results suggested that Notch4 play cell fate decision in vasculogenesis using the similar mechanism of the lateral inhibition.
We also attempted to analyze the components of Notch4 signaling pathway using an induction and differentiation system for endothelial cells from embryonic stem (ES) cells. Expression of Notch4 was observed in undifferentiated ES cells, and disappeared after induction. At the onset of endothelial cells differentiation Notch4 was re-expressed. We searched candidate genes with the same expression pattern as Notch4 by the Differential Display method. Several genes were identified to examine the interaction with Notch4.
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Report
(4 results)
Research Products
(2 results)
