568 Autophagy Controls Epidermal Tumour Formation and Hair Follicle Stem Cell Activation

Autophagy is a cellular recycling program that serves as a crucial survival pathway and controls inflammatory responses in a context-dependent manner. Here we demonstrate that ablation of autophagy selectively in keratinocytes, results in exacerbated skin inflammatory responses and a higher sensitivity to skin tumour formation. Autophagy-deficient keratinocytes are markedly sensitized to apoptosis and single-cell RNA-sequencing of age-matched skin with autophagy-proficient or -deficient keratinocytes reveals the unique presence of a ‘hair growth’ signature in autophagy-deficient keratinocytes. We noted precocious onset of hair follicle growth in mice lacking keratinocyte autophagy, indicating early activation of hair follicle stem cells. Together, our data demonstrate that keratinocyte autophagy is a crucial mechanism controlling hair follicle stem cell activation kinetics, skin inflammation and tumorigenesis.