| Project/Area Number |
18K08512
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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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| Review Section |
Basic Section 54040:Metabolism and endocrinology-related
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| Research Institution | Wakayama Medical University (2020)
Osaka University (2018-2019) |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
片上 直人 大阪大学, 医学系研究科, 講師 (10403049)
河盛 段 大阪大学, 医学系研究科, 助教 (50622362)
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2020: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2019: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2018: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | 膵β細胞再生 / インスリン転写因子 / 膵β細胞化 / 分化転換 / 膵β細胞 / 分化誘導 / 転写因子 |
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| Outline of Final Research Achievements |
It is possible to produce insulin-expressing cells in vivo by ectopic expression of transcription factors with Cre/loxP system. However, the efficiency of the reprograming toward pancreatic β-cell is still insufficient. In order to explore the optimal cells for that direct reprograming, we used several Cre mice to induce transcription factors in different candidate cells, and found better candidate tissue for producing β-cells which have glucose stimulated insulin secretion. Furthermore, from the point of view that there is developmentally unique timing for each transcription factors involved in β-cell differentiation, we are trying to construct the gene recombination system to shift the expression timing of transcription factors in non-β candidate cells in vivo.
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| Academic Significance and Societal Importance of the Research Achievements |
インスリン分泌の枯渇した糖尿病患者の根治のためには、膵β細胞機能補完の必要があり、幹細胞からβ細胞への分化誘導を促す再生医療が注目され、膵β細胞様細胞への分化誘導が可能となっているがいまだ高率といえず、意図しない細胞への分化や未分化状態の維持なども認められる。一方、本研究のような転写因子の異所性発現によるin vivoでの膵β細胞へのdirect reprogramingは、体内環境の利用や膵β細胞近縁細胞を母細胞とすることにより比較的効率的に膵β細胞様細胞の作製が可能である。分子生物学的手法による膵β細胞の作製という最終目標のため、さらなる効率化を目指した研究である。
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