LSD1 Is Critical for Epidermal Development and Skin Barrier Formation

The study provides evidence that Histone lysine-specific demethylase 1 (LSD1), an epigenetic enzyme, is crucial for skin development and barrier formation. LSD1, often overexpressed in human malignancies like cutaneous squamous cell carcinoma (cSCC), was found to be essential for proper epidermal stratification, hair follicle development, and functioning of the skin barrier in mice. Mice with an epidermal deletion of Lsd1 were embryonic lethal due to severe barrier dysfunction and a significant reduction in key epidermal barrier genes. Interestingly, Lsd1 deficiency led to an upregulation of Ovol2, a master transcription factor, suggesting a potential mechanism where Lsd1 regulates skin development by repressing Ovol2. These findings highlight the pivotal role of LSD1 in skin barrier establishment and offer new possibilities for LSD1 intervention in skin diseases characterized by abnormal barrier formation.