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Hair follicle aging is driven by transepidermal stem cell elimination via COL17A1 proteolysis

ABSTRACT: Hair loss is one of the typical aging phenotypes in mammals, yet the underlying mechanism(s) is unclear. Here we report that hair follicle stem cell (HFSC) aging causes the stepwise miniaturization of hair follicles and eventual hair loss both 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) to trigger “HFSC aging”, characterized by their loss of stemness signature and epidermal commitment. Those aged HFSCs are cyclically eliminated from the skin through their terminal epidermal differentiation, thereby causing hair follicle miniaturization. That process can be recapitulated by Col17a1 deficiency and prevented by forced maintenance of COL17A1 in HFSCs, demonstrating that stem cell homeostasis is the keystone against ultimate execution of the tissue/organ aging program.

ORGANISM(S): Mus musculus

PROVIDER: GSE72863 | GEO | 2015/12/01

SECONDARY ACCESSION(S): PRJNA295214

REPOSITORIES: GEO

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Obesity accelerates hair thinning by stem cell-centric converging mechanism [RNA-seq]

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