Stem Cell Regulation and Dynamics in Hair Follicle Regeneration and Aging
Description: 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.
Amount: ¥195,000,000
Funding type: research
Funder scheme: Grant-in-Aid for Scientific Research (S)
Start date: 2014-05-30
End date: 2019-03-31
Investigator: Emi NISHIMURA
Institution: Tokyo Medical and Dental University
Funded outputs count: 4
Funder award ID: 26221303
OpenAlex ID: G1392885397