2018 Fiscal Year Final Research Report
Cellular Stress and Fate Determination in Melanocyte Stem Cells
| Project Area | Establishing a new paradigm of the pathogenesis of diseases through the understanding of stem cell aging |
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| Project/Area Number |
26115003
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| Research Category |
Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)
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| Allocation Type | Single-year Grants |
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| Review Section |
Biological Sciences
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| Research Institution | Tokyo Medical and Dental University |
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Principal Investigator |
NISHIMURA Emi 東京医科歯科大学, 難治疾患研究所, 教授 (70396331)
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| Project Period (FY) |
2014-07-10 – 2019-03-31
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| Keywords | 幹細胞老化 / 幹細胞 / 再生 / 毛包 / 色素幹細胞 / 白髪 / 毛包幹細胞 / 脱毛 |
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| Outline of Final Research Achievements |
Hair graying and hair thinning are prominent aging phenotypes, yet the underlying mechanisms have been elusive. We previously found that hair follicle stem cells (HFSCs) provide a functional niche for melanocyte stem cells (McSCs). In vivo fate analysis of HFSCs revealed that the DNA damage response in HFSCs causes downregulation of type XVII collagen (COL17A1), a critical molecule for maintenance of HFSCs, to trigger HFSC aging and resultant hair follicle miniaturization. As COL17A1 is not expressed by McSCs but is critical for HFSCs to maintain McSCs, COL17A1 downregulation in HFSCs causes depletion of McSCs through their ectopic differentiation in the niche. The hair follicle aging process can be recapitulated by Col17a1 deficiency and prevented by the forced maintenance of COL17A1 in HFSCs, demonstrating that COL17A1 in HFSCs orchestrates the stem cell-centric aging program of the epithelial mini-organ and indicating potential angles for anti-ageing therapeutic intervention.
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| Free Research Field |
幹細胞生物学、老化生物学、皮膚科学
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| Academic Significance and Societal Importance of the Research Achievements |
本研究成果は、加齢性脱毛や白髪など典型的な老化形質の発現において組織幹細胞の加齢変化が中心的な役割を果たすこと、加齢によって品質の低下した幹細胞を効率よく生体から排除する仕組みが働くため幹細胞が枯渇し、その結果、器官自体が矮小化し、毛を生やしたり色素を沈着させるなどの機能が低下することを世界に先駆けて解明した。また本成果に基づく組織幹細胞の枯渇を防ぐ抗老化技術ならびに再生促進技術の開発は超高齢化社会において健康促進へと繋がるものと期待できる。
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