2022 Fiscal Year Final Research Report
Elucidation of bile duct development and its disorder mechanism using biliary atresia-specific iPS cells
| Project/Area Number |
20K08977
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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 55010:General surgery and pediatric surgery-related
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| Research Institution | Dokkyo Medical University (2022)
The University of Tokyo (2020) |
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Principal Investigator |
Suzuki Kan 獨協医科大学, 医学部, 准教授 (80598508)
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| Co-Investigator(Kenkyū-buntansha) |
木戸 丈友 東京大学, 定量生命科学研究所, 特任講師 (00401034)
藤代 準 東京大学, 医学部附属病院, 教授 (60528438)
林 洋平 国立研究開発法人理化学研究所, バイオリソース研究センター, チームリーダー (90780130)
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| Project Period (FY) |
2020-04-01 – 2023-03-31
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| Keywords | biliary atresia / BA specific iPS cell / whole genome analysis / hepatic progenitor cell / pathophysiology |
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| Outline of Final Research Achievements |
We established iPS cells from peripheral blood mononuclear cells of 6 biliary atresia (BA) patients, and completed their characterization and whole-genome analysis. Furthermore, it was shown that the established BA-specific iPS cells can be induced into CPM-positive hepatic progenitor cells and biliary epithelial cells.
On the other hand, we found approximately 3,000 SNP mutations and polymorphisms that were duplicated in more than 2 patients from the whole genome analysis data, and narrowed down the genes that have abnormalities in the liver and gallbladder of the gene-disrupted mice. 22 genes which have relation to BA pathophysiology were identified. In addition,iin one patient, we identified a specific deletion site by virtual karyotyping analysis and confirmed that the gene encoded by the site was expressed in Kupffer cells.
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| Free Research Field |
Pediatric Surgery
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| Academic Significance and Societal Importance of the Research Achievements |
いまだに明らかな原因が不明である胆道閉鎖症の病態解明に向けて、疾患特異的iPS細胞と全ゲノム解析を組み合わせて関連遺伝子を探索した。本研究期間に、病態解明に向けた研究の基盤となる胆道閉鎖症特異的iPS細胞の樹立方法が確立され、さらに樹立した胆道閉鎖症特異的iPS細胞から胆管上皮細胞への誘導が可能であることを示しこの細胞ソースが今後の研究に使用可能であることを示した。また、多因子が想定される胆道閉鎖症発症に関連する可能性がある遺伝子を複数同定した。
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