2021 Fiscal Year Final Research Report
Molecular elucidation of two-step maturation process using immature pancreatic beta cell lines
| Project/Area Number |
19K09002
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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 | Osaka University |
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Principal Investigator |
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| Project Period (FY) |
2019-04-01 – 2022-03-31
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| Keywords | 膵β細胞 / 転写因子 / インスリン分泌 / 成熟機構 |
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| Outline of Final Research Achievements |
The Mafa gene encoding a transcription factor has been implicated in the functional maturation and insulin secretory capacity of beta cells and also in the pathogenesis of diabetes. In this study, immature beta cell lines lacking the Mafa gene and Mafa-rescue beta cell lines were used to search for candidate genes and factors involved in maturation and maintenance of beta cells. Effects of overexpression of the candidate genes and exposure to various external stimuli on the functional maturation were examined in Mafa-KO beta cells. Gene expression patterns of a Mafa-deficient beta cell line isolated from the newly established functionally mature MIN6-CB4 cell line and its rescue beta cell line were analyzed by RNA sequencing.
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| Free Research Field |
糖尿病学
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| Academic Significance and Societal Importance of the Research Achievements |
本研究は、未成熟Mafa欠損β細胞株において、Mafa発現後にさらに成熟させるために必要な因子を探索することを目的としている。膵島から未成熟なβ細胞のみを単離培養することは困難であるため、この細胞株なしには、in vitro系において成熟機構を解析することは難しい。この細胞をもちいた研究により得られる知見は、iPS細胞などの幹細胞を高度に成熟したインスリン産生細胞に分化誘導する技術の実用化に応用できると期待される。
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