Unraveling the Comedone Switch Through Single-Cell Resolution of Human Acne Lesions

This study investigates the molecular events initiating acne vulgaris by examining human acne lesions at single-cell resolution. Researchers integrated single-cell transcriptomic data from healthy skin, non-lesional skin of acne patients, and lesional acne tissue to explore the early stages of comedogenesis. They discovered a previously uncharacterized cell population in non-lesional skin resembling a microcomedone and mapped its transcriptional architecture. The study provides data-driven evidence for the comedone switch hypothesis, showing a shift from sebaceous to infundibular cell fate, characterized by enhanced keratinization and inflammatory programs. Additionally, broader epithelial changes were noted, including the loss of POSTN and ERRFI1 expression in basal interfollicular epidermal keratinocytes. These findings offer a detailed framework for understanding human comedogenesis and suggest mechanisms linking genetic susceptibility, environmental factors, and lineage imbalance in the upper hair follicle.