ΔNp63 Regulates Homeostasis, Stemness, and Suppression of Inflammation in the Adult Epidermis.

The p63 transcription factor is critical for epidermis formation in embryonic development, but its role in the adult epidermis is poorly understood. In this study, we show that acute genetic ablation of ΔNp63, the main p63 isoform, in adult epidermis disrupts keratinocyte proliferation and self-maintenance and, unexpectedly, triggers an inflammatory psoriasis-like condition. Mechanistically, single-cell RNA sequencing revealed the downregulation of cell cycle genes, upregulation of differentiation markers, and induction of several proinflammatory pathways in ΔNp63-ablated keratinocytes.