Analyses of the mechanisms for development of sensory epithelia in cochleae and vestibula and application to generating the model for deafness using hiPSC
| Project/Area Number |
18K09318
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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 56050:Otorhinolaryngology-related
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| Research Institution | Kyoto University |
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Principal Investigator |
Ohnishi Hiroe 京都大学, 医学研究科, 特定助教 (50397634)
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| Co-Investigator(Kenkyū-buntansha) |
石川 正昭 京都大学, 医学研究科, 客員研究員 (10813743)
中川 隆之 京都大学, 医学研究科, 研究員 (50335270)
宮本 達雄 山口大学, 大学院医学系研究科, 教授 (40452627)
山本 典生 京都大学, 医学研究科, 准教授 (70378644)
田浦 晶子 藍野大学, 医療保健学部, 教授 (70515345)
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| Project Period (FY) |
2018-04-01 – 2023-03-31
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| Project Status |
Completed (Fiscal Year 2022)
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| Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | ヒトiPS細胞 / 蝸牛 / 難聴モデル / 前庭 / オルガノイド / 内耳 / iPS細胞 / 内耳オルガノイド / 分化誘導 / 内耳感覚上皮細胞 / トランスクリプトーム解析 / ゲノム編集 |
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| Outline of Final Research Achievements |
The purpose of this study was to identify genes and signaling pathways specific to cochlear sensory epithelial development and to establish a method to induce cochlear sensory epithelial cell induction derived from human iPS cells by regulating these genes and pathways, and to generate in vitro models necessary to analyze the mechanism of hearing loss and establish therapeutic methods. To this end, we confirmed the expression sites of the identified cochlear-specific expressed genes and examined their changes with age in days to confirm their effectiveness as markers. In parallel, we optimized the conditions for the generation of genome-edited human iPS cells necessary for the establishment of a cochlear-type sensory epithelium induction method and improved the efficiency of inner ear organoid induction by examining conditions using ATOH1-GFP hiPS cells, establishing the basic elements and technology necessary for the induction of cochlear sensory epithelial cell differentiation.
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| Academic Significance and Societal Importance of the Research Achievements |
老化や騒音等、様々な原因により感音難聴が起こるが、それに対する確実な予防効果、治療効果のある薬剤は開発されていない。発生後の哺乳類の蝸牛感覚上皮は一度障害されると再生しない。治療薬の開発には適切なin vitroモデルが必要であるが、ヒト蝸牛細胞の初代培養を研究に用いることはできず、適切な細胞株も存在しないため、スクリーニングに使用可能なヒト細胞モデルの確立が望まれる。本研究ではそのヒト細胞モデルとしてヒトiPS細胞由来蝸牛感覚上皮の誘導法確立に必須の基礎となる誘導法の導入と指標となる分子の同定を行った。この結果は今後の難聴予防・治療薬の開発に寄与するものであると考えられる。
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Report
(6 results)
Research Products
(2 results)
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[Presentation] Trial for Improvement of Hair Cell Induction Method from Human Induced Pluripotent Stem Cell2019
Author(s)
Ohnishi H, Skerleva D, Okuyama H, Miyamoto T, Matsuura S, Kirino K, Yamamoto N, Ito J, Omori K, Saito M, Tsukita K, Inoue H and Nakagawa T.
Organizer
Association for Research in Otolaryngology 42th MidWinter Meeting
Related Report
Int'l Joint Research
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