Stem cells: Hair follicle aging is driven by transepidermal elimination of stem cells via COL17A1 proteolysis

Hiroyuki Matsumura; Yasuaki Mohri; Nguyen Thanh Binh; Hironobu Morinaga; Makoto Fukuda; Mayumi Ito; Sotaro Kurata; Jan Hoeijmakers; Emi K. Nishimura

doi:10.1126/science.aad4395

Stem cells: Hair follicle aging is driven by transepidermal elimination of stem cells via COL17A1 proteolysis

Hiroyuki Matsumura, Yasuaki Mohri, Nguyen Thanh Binh, Hironobu Morinaga, Makoto Fukuda, Mayumi Ito, Sotaro Kurata, Jan Hoeijmakers, Emi K. Nishimura

Onderzoeksoutput: Bijdrage aan tijdschrift › Artikel › peer review

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Hair thinning and loss are prominent aging phenotypes but have an unknown mechanism. We show 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.

Originele taal-2	Engels
Artikelnummer	aad4395
Tijdschrift	Science
Volume	351
Nummer van het tijdschrift	6273
DOI's	https://doi.org/10.1126/science.aad4395
Status	Gepubliceerd - 5 feb. 2016
Extern gepubliceerd	Ja

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@article{ecd104319ba54b9bb6a86fd55906145d,

title = "Stem cells: Hair follicle aging is driven by transepidermal elimination of stem cells via COL17A1 proteolysis",

abstract = "Hair thinning and loss are prominent aging phenotypes but have an unknown mechanism. We show 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.",

author = "Hiroyuki Matsumura and Yasuaki Mohri and {Thanh Binh}, Nguyen and Hironobu Morinaga and Makoto Fukuda and Mayumi Ito and Sotaro Kurata and Jan Hoeijmakers and Nishimura, {Emi K.}",

year = "2016",

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day = "5",

doi = "10.1126/science.aad4395",

language = "English",

volume = "351",

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T2 - Hair follicle aging is driven by transepidermal elimination of stem cells via COL17A1 proteolysis

AU - Matsumura, Hiroyuki

AU - Mohri, Yasuaki

AU - Thanh Binh, Nguyen

AU - Morinaga, Hironobu

AU - Fukuda, Makoto

AU - Ito, Mayumi

AU - Kurata, Sotaro

AU - Hoeijmakers, Jan

AU - Nishimura, Emi K.

PY - 2016/2/5

Y1 - 2016/2/5

N2 - Hair thinning and loss are prominent aging phenotypes but have an unknown mechanism. We show 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.

AB - Hair thinning and loss are prominent aging phenotypes but have an unknown mechanism. We show 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.

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Stem cells: Hair follicle aging is driven by transepidermal elimination of stem cells via COL17A1 proteolysis

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