1397 LSD1 is critical for epidermal development and skin barrier formation

Histone lysine-specific demethylase 1 (LSD1) is a key epigenetic enzyme known to be involved in lineage-specific development and cell differentiation. Through its function, LSD1 represses crucial differentiation genes preserves progenitor-like fates. As such, frequently overexpressed human malignancies, portending poor prognosis cancers including cutaneous squamous carcinoma (cSCC). inhibitors show significant promise the treatment of cSCC, underscoring need have better understanding LSD1’s role skin homeostasis development. Previously, our lab demonstrated that inhibition vitro unleashes an epidermal program prevent cSCC (Egolf & Aubert, Cell Reports, 2019). However, it virtually unknown how functions vivo. Here, we provide evidence for as essential regulator Mice with deletion Lsd1 are embryonic lethal stemming from profound barrier dysfunction, lack proper stratification, impaired hair follicle Utilizing RNA-sequencing, deficiency results dramatic reduction genes. Intriguingly, several these include those lipid processing. In contrast, find upregulates Ovol2, master transcription factor, suggesting potential mechanism whereby orchestrates through repression Ovol2. Taken together, data supports pivotal establishing barrier, providing insight into regulation This also opens avenues intervention diseases characterized by aberrant formation.