New method for establishing self-renewing megakaryocyte cell lines using iPS cells
| Project/Area Number |
18K18365
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 90110:Biomedical engineering-related
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| Research Institution | Kyoto University |
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Principal Investigator |
Nakamura Sou 京都大学, iPS細胞研究所, 特定拠点助教 (50769833)
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| Project Period (FY) |
2018-04-01 – 2022-03-31
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| Project Status |
Completed (Fiscal Year 2021)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2021: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2020: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
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| Keywords | 巨核球 / iPS細胞 / imMKCL / iPS / 血小板 / 自己複製 / c-MYC / 巨核球分化 / 再生医療 |
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| Outline of Final Research Achievements |
RNA-seq analysis of several megakaryocyte cell lines displaying different proliferative capabilities enabled to identify the responsible genes that inhibit self-renewal ability in megakaryocyte cell lines. Furthermore, alternative vector system was applied to generate megakaryocyte cell lines, whereby epigenetic modifications were silenced at the stage of hematopoietic cell differentiation from pluripotent stem cells. Such improvements allowed us to generate megakaryocyte cell lines from several human iPS cell clones, contributing to high efficiency of megakaryocyte cell line induction.
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| Academic Significance and Societal Importance of the Research Achievements |
同種免疫性の血小板輸血不応症を発症する患者では、HLA/HPAが適合するドナーの確保が必要であるが、稀な型の場合や緊急時は供給不足が危惧される。解決策として、申請者らは、iPS細胞から分化誘導した血小板前駆細胞、巨核球を細胞株化し、産業化可能な血小板製造法を確立したが、安定増殖株の樹立効率が低いことが課題となっていた。本研究で明らかとなった巨核球細胞株自己複製抑制機構を解除する方法を新規ベクターシステムに新たに組み込むことで、個性の異なる複数のiPS細胞クローン由来不死化巨核球の作製効率を飛躍的に改善することができるため、HLA/HPA一致血小板製剤供給源の問題点を解決する可能性が提示できた。
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Report
(5 results)
Research Products
(8 results)
