| Project/Area Number |
16K09766
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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 |
Metabolomics
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| Research Institution | Juntendo University |
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Principal Investigator |
Miyatsuka Takeshi 順天堂大学, 医学(系)研究科(研究院), 准教授 (60622363)
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| Research Collaborator |
SASAKI shugo
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | β細胞 / シングルセルトランスクリプトーム解析 / トランスクリプトーム解析 / 蛍光イメージング / 糖尿病再生医療 / 膵発生 / β細胞新生 / シングルセルRNA-seq解析 / spatiotemporal analysis / single-cell RNA-seq / beta cells neogenesis / reporter mouse / 糖尿病 / 再生医学 |
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| Outline of Final Research Achievements |
We developed the novel mouse model “Ins1-eGFP; Timer” that provides spatiotemporal information of newly generated β cells.
Fluorescent imaging revealed that some newborn β cells are detected close to the pancreatic ducts (βduct cells), and unexpectedly, all the other newborn β cells were observed away from the ductal structures and were adjacent to blood vessels (βvessel cells) and pre-existing islets. More βduct cells expressed Mafb, whereas more βvessel cells expressed Mafa, showing distinct characteristics of two cell types of newborn β cells. Furthermore, single-cell RNA sequencing also confirmed transcriptional heterogeneity of newborn β cells.
Collectively, both histological imaging and single-cell transcriptome analysis demonstrated spatial and transcriptional heterogeneity of β-cell neogenesis during development, which will lead to a better understanding of β-cell neogenesis for future cell therapy.
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| Academic Significance and Societal Importance of the Research Achievements |
新たに開発したレポーターマウスを用いて生まれたばかりβ細胞を標識しながら蛍光イメージングを行った結果、従来から考えられてきた膵管近傍で生まれる“βduct細胞”以外に、血管近傍で生まれる“βvessel細胞”が存在し、遺伝子発現パターンも異なることが明らかとなった。さらに新生β細胞の遺伝子発現プロファイルを１細胞レベルで解析した結果、新生β細胞は５つのクラスターに細分化されることが示された。
これらの知見が糖尿病根治を目指したβ細胞再生医療に応用されることを期待したい。
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