Induction of hematopoietic stem/progenitor cells from mouse pluripotent stemceIIsby inhibitionofanadaptor protein, Lnk.
| Project/Area Number |
23790123
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Biological pharmacy
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| Research Institution | 独立行政法人医薬基盤研究所 |
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Principal Investigator |
TASHIRO Katsuhisa 独立行政法人医薬基盤研究所, 創薬基盤研究部幹細胞制御プロジェクト, 研究員 (30580138)
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| Research Collaborator |
KAWABATA Kenji 独立行政法人医薬基盤研究所, 創薬基盤研究部幹細胞制御プロジェクト, プロジェクトリーダー
MIZUGUCHI Hiroyuki 大阪大学, 大学院・薬学研究科, 教授
SAKURAI Fuminori 大阪大学, 大学院・薬学研究科, 准教授
YAMAGUCHI Tomoko 独立行政法人医薬基盤研究所, 創薬基盤研究部幹細胞制御プロジェクト, プロジェクト研究員
OMORI Miyuki 大阪大学, 大学院・薬学研究科, 大学院生
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| Project Period (FY) |
2011 – 2012
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| Project Status |
Completed (Fiscal Year 2012)
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| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2012: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2011: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
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| Keywords | ES細胞 / ips細胞 / 血液細胞 / 再生医学 / 多能性幹細胞 / 分化誘導 / 幹細胞 |
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| Research Abstract |
The adaptor protein Lnk is shown to negatively regulate HSPC function and HSPCs derived from Lnk-deficient mice show enhanced self-renewal and repopulation capacity. In this study, we attempted to generate hematopoietic cells including HSPCs from mouse embryonic stem(ES)cells and induced pluripotent stem(iPS)cells by inhibition of Lnk function using a dominant-negative mutant of Lnk(DN-Lnk)gene. We showed that Lnk inhibition in mouse ES cells and iPS cells resulted in more efficient generation of mesodermal cells and hematopoietic cells than control cells. Lnk inhibition by the transduction of DN-Lnk gene augmented the thrombopoietin-induced phospholylation of Jak2, Erk1/2, and Akt, indicating the enhanced sensitivity to TPO. Thus, our data clearly showed that inhibition of Lnk in ES cells and iPS cells could lead to efficient generation and expansion of immature hematopoietic cells.
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Report
(3 results)
Research Products
(15 results)
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[Journal Article] Efficient Generation of Functional Hepatocytes from Human Embryonic Stem Cells and Induced luripotent Stem Cells by HNF4αTransduction2012
Author(s)
Takayama K, Inamura M., Kawabata K., Katayama K, Higuchi M., Tashiro K, Nonaka A., Sakurai F., Hayakawa T., Furue MK., Mizuguchi H
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Journal Title
Mol. Ther
Volume: 20(1)
Pages: 127-137
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