| Project/Area Number |
16K20293
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Otorhinolaryngology
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| Research Institution | Kyoto University (2018)
Research Institute, Shiga Medical Center (2016-2017) |
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Principal Investigator |
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| Research Collaborator |
Dabdoub Alain
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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 |
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2018: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2017: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | ダイレクトリプログラミング / 蝸牛神経 / 転写因子 / ラセン神経節 / シュワン細胞 / グリア細胞 / 非グリア細胞 / 分化転換 / Competence / ラセン神経節シュワン細胞 / 神経分化誘導 / ラセン神経節細胞 / 再生医学 / 耳科学 / 細胞・組織 / 神経科学 |
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| Outline of Final Research Achievements |
We converted endogenous cells into replacement primary auditory neurons using gene therapy to ameliorate hearing loss. Recent reports have demonstrated that somatic mouse cells and glial cells can be directly converted to functional neurons by overexpression of transcription factors in vitro and in vivo. Moreover, induced neurons can be directed towards distinct neuronal phenotypes when the appropriate transcriptional cues are provided with the conversion factors. A target cell population for endogenous regeneration and induction is the spiral ganglion glial cells which surround auditory neurons and survive after neuron degeneration. We generated functional induced neurons from spiral ganglion glial cells in vitro. Serendipitously, we found out murine type II auditory neurons highly expressed Gata3, which is a known transcription factor expressed in embryonic primary auditory neurons, even in adulthood.
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| Academic Significance and Societal Importance of the Research Achievements |
高度難聴患者に対しては補聴器、重度難聴患者には人工内耳が臨床では用いられているが、いずれも難聴を根本的に治療する方法ではない。本研究の成果は、聴神経に存在する内在性のグリア細胞から聴神経類似の神経細胞を作製したことである。すなわち、本研究は一次聴神経が生体内でも再生される可能性があることを示唆し、その場合、補聴器、人工内耳の効果が高まるのみならず、それらの機械の使用を不要とする新規難聴治療法開発の端緒となる可能性がある。
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