Histone H3 K4/9/27 Trimethylation Levels Affect Wound Healing and Stem Cell Dynamics in Adult Skin

The study explored the role of histone H3 K4/9/27 trimethylation in adult skin stem cell dynamics and wound healing. It was found that hypomethylation of these histones in mouse skin and hair follicle stem cells (HFSCs) preceded hair growth. Inhibiting histone demethylases impaired hair follicle differentiation and growth, delayed wound healing, and affected epithelial cell differentiation and blood vessel recruitment, though not cell proliferation or fibroblast recruitment. The study used Aspm-CreER and Lgr5-CreER tools to show reduced contributions of skin and hair follicle lineages to wound healing when hypomethylation was blocked. This blockage increased BMP4 expression and upregulated H3 K4me3 on the Bmp4 promoter, affecting HFSC quiescence, hair cycle, and injury repair. The findings suggested that transient hypomethylation of histone H3 K4/9/27me3 was crucial for maintaining proper tissue homeostasis and repair in adult skin.