Disrupted cholesterol biosynthesis and hair follicle stem cell impairment in the onset of alopecia

The study investigates the impact of disrupted cholesterol biosynthesis on hair follicle stem cells (HFSCs) and hair follicle cycling, particularly in primary cicatricial alopecia (PCA). It was found that patients with PCA exhibit decreased expression of HFSC marker genes, and experiments with 7-dehydrocholesterol and a cholesterol biosynthesis inhibitor in mice and organoid cultures showed impaired hair regrowth and increased apoptosis in stem cells. These findings highlight the crucial role of cholesterol production in maintaining HFSC integrity and suggest that sterol intermediates play a significant role in hair follicle cycling and stem cell function. The study concludes that aberrant cholesterol production leads to irreversible hair follicle damage and impaired hair regrowth in PCA.