| Project/Area Number |
17K09911
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Hematology
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| Research Institution | Tokyo Metropolitan Institute of Medical Science |
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Principal Investigator |
KITAJIMA Kenji 公益財団法人東京都医学総合研究所, 生体分子先端研究分野, 主席研究員 (10346132)
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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| Keywords | 造血幹細胞 / ES細胞 / 細胞分化 / インターフェロン / 分化誘導 / 炎症性サイトカイン / 発生・分化 / 再生医学 |
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| Outline of Final Research Achievements |
In mouse embryos, hematopoietic stem cells (HSCs) are differentiated from hemogenic endothelial cells (HECs) via pro-HSCs and pre-HSCs. We found that the cells phenotypically identical to those cells could be induced from mouse embryonic stem cells (ESCs) by co-culture with OP9 stromal cells. In AGM regions, inflammatory cytokines are involved in HSC development. Therefore in vitro-differentiated HECs from ESCs were treated with Interferon-gamma. Consequently, Lin-Sca-1+c-Kit+ (LSK) cells were significantly induced. However, these LSK cells were not engraftable when transplanted into irradiated recipient mice. Thus, engraftable HSCs could not be obtained from mouse ESCs.
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| Academic Significance and Societal Importance of the Research Achievements |
マウスESCsから様々な血液細胞をin vitroで誘導することができるが、現在まで、遺伝子操作なしでHSCsへ分化誘導する方法の開発には誰も成功していない。この原因は、AGM領域に存在するHSC分化誘導因子がin vitroでは欠けている可能性が考えられる。マウスESCsからHSCsをin vitroで分化誘導できる因子の同定は、哺乳類胚発生におけるHSC発生機構の理解につながるものであり学術的意義は高い。また、ヒト人工多能性幹細胞（iPSCs）からin vitroでHSCsへ分化誘導する培養法の開発にも繋がるものであり、iPSCsを利用した再生医療などへの応用も期待できる。
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