{Reference Type}: Journal Article
{Title}: IRX5 promotes DNA damage repair and activation of hair follicle stem cells.
{Author}: Chen JK;Wiedemann J;Nguyen L;Lin Z;Tahir M;Hui CC;Plikus MV;Andersen B;
{Journal}: Stem Cell Reports
{Volume}: 18
{Issue}: 5
{Year}: 2023 05 9
{Factor}: 7.294
{DOI}: 10.1016/j.stemcr.2023.03.013
{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 DNA damage in Irx5-/-mice. Consistent with a role for IRX5 as a promoter of DNA damage repair, we find that IRX genes are upregulated in many cancer types and that there is a correlation between IRX5 and BRCA1 expression in breast cancer.