IRX5 promotes DNA damage repair and activation of hair follicle stem cells.

ABSTRACT: The molecular mechanisms allowing hair follicles to periodically activate their stem cells (HFSCs) are incompletely characterized. Here, we identify the transcription factor IRX5 as a promoter of HFSC activation. Irx5^-/- mice have delayed anagen onset, with increased DNA damage and diminished HFSC proliferation. Open chromatin regions form near cell cycle progression and DNA damage repair genes in Irx5^-/- HFSCs. DNA damage repair factor BRCA1 is an IRX5 downstream target. Inhibition of FGF kinase signaling partially rescues the anagen delay in Irx5^-/- mice, suggesting that the Irx5^-/- HFSC quiescent phenotype is partly due to failure to suppress Fgf18 expression. Interfollicular epidermal stem cells also show decreased proliferation and increased

SUBMITTER: Chen JK 

PROVIDER: S-EPMC10202659 | biostudies-literature | 2023 May

REPOSITORIES: biostudies-literature