Stem Cell Regulation and Dynamics in Hair Follicle Regeneration and Aging

2018 Fiscal Year Final Research Report

• Project/Area Number: 26221303
• Research Category: Grant-in-Aid for Scientific Research (S)
• Allocation Type: Single-year Grants
• Research Field: Experimental pathology
• Research Institution: Tokyo Medical and Dental University
• Principal Investigator: NISHIMURA Emi 東京医科歯科大学, 難治疾患研究所, 教授 (70396331)
• Co-Investigator(Kenkyū-buntansha): 松村 一 東京医科大学, 医学部, 主任教授 (80256263)
• Project Period (FY): 2014-05-30 – 2019-03-31
• Keywords: 再生 / 老化 / 幹細胞 / 自己複製 / 毛 / 脱毛 / COL17A1

Outline of Final Research Achievements

Hair thinning and loss are prominent aging phenotypes but have an unknown mechanism. We showed that hair follicle stem cell (HFSC) aging causes the stepwise miniaturization of hair follicles and eventual hair loss in wild-type mice and in humans. In vivo fate analysis of HFSCs revealed that the DNA damage response in HFSCs causes proteolysis of type XVII collagen (COL17A1/BP180), a critical molecule for HFSC maintenance, to trigger HFSC aging, characterized by the loss of stemness signatures and by epidermal commitment. Aged HFSCs are cyclically eliminated from the skin through terminal epidermal differentiation, thereby causing hair follicle miniaturization. The 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.

Free Research Field

幹細胞生物学、皮膚科学、実験病理学、老化生物学

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をモデルとして、組織幹細胞の加齢変化が器官老化において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、器官を構成している機能細胞群も全体として減少すること、これによって器官自体も小型化し機能低下に至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長寿の延伸へと繋がるものと期待できる。