2023 Fiscal Year Final Research Report
Comprehensive CRISPE screening of functional gene in osteoimmune cells
| Project/Area Number |
21K18254
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| Research Category |
Grant-in-Aid for Challenging Research (Pioneering)
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| Allocation Type | Multi-year Fund |
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| Review Section |
Medium-sized Section 49:Pathology, infection/immunology, and related fields
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| Research Institution | The University of Tokyo |
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Principal Investigator |
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| Project Period (FY) |
2021-07-09 – 2024-03-31
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| Keywords | CRISPR / 骨免疫 |
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| Outline of Final Research Achievements |
In this study, we aimed to identify genes that regulate osteoimmune cell differentiation and function by employing CRISPR/Cas9 screening. Based on in sillico and in vitro analysis, we identified a novel transcription factor that regulates osteoclast differentiation. We determined the enhancer regions that regulate RANKL expression and validated them using genetically modified mice to elucidate the physiological and pathological significance of the each of RANKL enhancers. This study has further advanced our understanding of osteoimmunology and led to the development of new therapeutic strategies.
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| Free Research Field |
免疫学
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| Academic Significance and Societal Importance of the Research Achievements |
高齢化が進む日本社会において、関節炎や歯周炎、骨粗鬆症は生活の質を損なう要因であり、解決しなければならない問題である。本研究により、新規破骨細胞制御因子の同定や新たなRANKLの発現制御機構の一旦が解明されたことで、骨免疫の理解が進んだだけでなく、これらの疾患に関連する新たな治療戦略の開発につながった。また、本アプローチが細胞機能に重要な遺伝子の同定に極めて有効であることが示された。本手法を血液細胞全般に応用することで、さらなる医学的重要知見がもたらされると考えられる。
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