| Project/Area Number |
20K22659
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| Research Category |
Grant-in-Aid for Research Activity Start-up
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| Allocation Type | Multi-year Fund |
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| Review Section |
0702:Biology at cellular to organismal levels, and related fields
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| Research Institution | University of Tsukuba (2022)
Kumamoto University (2020-2021) |
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Principal Investigator |
Raja Erna 筑波大学, 生存ダイナミクス研究センター, 助教 (30770581)
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| Project Period (FY) |
2020-09-11 – 2023-03-31
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| Project Status |
Completed (Fiscal Year 2022)
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| Budget Amount *help |
¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
Fiscal Year 2021: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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| Keywords | skin aging / wound healing / regeneration / extracellular matrix / cell signalling / fibulin 7 / stem cells heterogeneity / epidermal stem cells / ECM / stem cells / aging / heterogeneity |
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| Outline of Research at the Start |
The molecular drivers of skin stem cell aging are largely unknown. Aging skin stem cells lose their heterogeneity and Fibulin-7 is a potential regulator. We aim to unravel Fibulin-7 mechanism of action of by identifying its binding partners, signaling pathways and the function of these interactions.
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| Outline of Final Research Achievements |
By long term lineage tracing, we found that the fast-cycling epidermal stem cells are depleted during chronological skin aging while the slow-cycling counterparts are maintained. Interestingly, fibulin 7 ECM expression which is localized to the epidermal basement membrane, is reduced in aged skin. Mice lacking fibulin 7 expression exhibited early skin aging-like traits such as loss of fast-cycling stem cells, alterations in basement membrane-associated proteins such as Collagen IV, laminins and Collagen XVII, and aberrant differentiation state. Mechanistically, fibulin 7 keeps a slower epidermal stem cell proliferation in the young adult skin and this may contribute to minimize the accumulation of replication stress and early stem cell depletion.
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| Academic Significance and Societal Importance of the Research Achievements |
私達は、表皮幹細胞の老化の特徴を明らかにし、皮膚における機能が知られていなかったfibulin 7が、どのように恒常性を維持し、増殖周期の遅い幹細胞集団と増殖周期の速い幹細胞集団のバランスを調節することで、老化のプロセスを制御するのか明らかにした。この知見は、皮膚の老化についての理解を深め、慢性創傷などの皮膚疾患の治癒に繋がると考えられる。
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