Generation of human iPS-derived pancreatic beta cells and its application towards regenerative medicine
| Project/Area Number |
26253059
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Metabolomics
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| Research Institution | Tokyo Institute of Technology |
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Principal Investigator |
Kume Shoen 東京工業大学, 生命理工学院, 教授 (70347011)
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| Co-Investigator(Kenkyū-buntansha) |
荒木 喜美 熊本大学, 学内共同利用施設等, 教授 (90211705)
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| Project Period (FY) |
2014-04-01 – 2017-03-31
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| Project Status |
Completed (Fiscal Year 2016)
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| Budget Amount *help |
¥41,340,000 (Direct Cost: ¥31,800,000、Indirect Cost: ¥9,540,000)
Fiscal Year 2016: ¥12,740,000 (Direct Cost: ¥9,800,000、Indirect Cost: ¥2,940,000)
Fiscal Year 2015: ¥13,520,000 (Direct Cost: ¥10,400,000、Indirect Cost: ¥3,120,000)
Fiscal Year 2014: ¥15,080,000 (Direct Cost: ¥11,600,000、Indirect Cost: ¥3,480,000)
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| Keywords | 多能性幹細胞 / 分化誘導 / 糖尿病 / 再生医療 / 膵臓 / 代謝 / 増殖 / モノアミン / ドパミン / インスリン / 化合物 / 再生医学 / 膵β細胞 / 膵臓β細胞 |
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| Outline of Final Research Achievements |
Through screening and analysis of small molecular compound that potentiated differentiation of human induced pluripotent stem (hiPS) cells into pancreatic beta cells, we found that activation of Wnt signal increased beta cell differentiation in hiPS cells, and that our previously identified VMAT2-monoamine as a negative regulator for pancreatic differentiation, also applied to hiPS cells. We also identified domperidone (DPD), a dopamine D2 receptor (DRD2) antagonist, as a compound that enhances beta cell mass. In adult islet dissociation cultures, beta cell loss occurs through dedifferentiation, which was prevented by DPD. Dopamine modulates beta cell mass through DRD2 and exerts an inhibitory effect on adenosine signaling, a previously identified beta cell mass positive regulator. We believe that our knowledge on regulation of beta cell differentiation and cell mass regulation would be profitable for future manipulation of hiPS-derived beta cells.
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Report
(4 results)
Research Products
(54 results)
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[Journal Article] Methionine metabolism regulates maintenance and differentiation of human pluripotent stem cells.2014
Author(s)
Shiraki, N., Shiraki, Y., Tsuyama, T., Obata, F., Miura, M., Nagae, G., Aburatani, H., Kume, K., Endo, F., and Kume, S.
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Journal Title
Cell Metab.
Volume: 19
Issue: 5
Pages: 780-794
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Journal Article] VMAT2 identified as a regulator of late-stage beta cell differentiation.2013
Author(s)
Sakano, D., Shiraki, N., Kikawa, K., Yamazoe, T., Kataoka, M., Umeda, K., Araki, K., Mao, D., Matsumoto, S., Nakagata, N., Andersson, O., Stainier, D., Endo, F., Kume, K., Uesugi, M. and Kume, S.
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Journal Title
Nat. Chem. Biol.
Volume: 10
Issue: 2
Pages: 141-148
DOI
Related Report
Peer Reviewed
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