2021 Fiscal Year Final Research Report
Origins of senescent cells that regulate aging in vivo
| Project/Area Number |
20K21497
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| Research Category |
Grant-in-Aid for Challenging Research (Exploratory)
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| Allocation Type | Multi-year Fund |
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| Review Section |
Medium-sized Section 48:Biomedical structure and function 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) |
2020-07-30 – 2022-03-31
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| Keywords | 細胞老化 / p16 / シングルセル解析 |
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| Outline of Final Research Achievements |
This study aims to identify senescent cells in individuals and analyze these cells at the single-cell level to determine the origin of senescent cells and their role in individual aging. Mice were generated in which p16-positive cells could be fluorescently stained with tdTomato in the presence of tamoxifen by insertion of CreERT2 into Exon1 at the p16Ink4a locus, currently the most reliable senescent cell marker.At the same time, DTR was also inserted to generate mice capable of selectively removing p16-positive cells in a diphtheria toxin (DT)-dependent manner. Using these mice, tdTomato-positive cells were isolated from various organs and tissues and subjected to single-cell transcriptome analysis. The results showed that senescent cells originated from various cell types and had diverse properties. Furthermore, their removal by DT improved the pathologies associated with various aging and lifestyle-related diseases.
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| Free Research Field |
分子腫瘍学
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| Academic Significance and Societal Importance of the Research Achievements |
細胞老化が様々な加齢性変化や生活習慣病に関わっていることが報告されているが、細胞老化研究は試験管内の解析が主であり、個体内のいつ、どこで、どのような性質を持っているのか全く分かっていなかった。このことから、個体老化や生活習慣病病態がどの様に老化細胞により制御されているのか全く不明であった。本研究により、世界で初めて一細胞レベルで老化細胞を解析可能なマウスが作製され、その解析から老化細胞の起源は多様であり、又それらの性質も起源となる細胞依存的に非常に不均一であることが分かった。これらの成果は、今後老化細胞により個体老化がどの様に制御されるのかを理解する上で非常に重要な知見を与えるものとなった。
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