1356 Wound memory predisposes to tumorigenesis

It is known that epidermal cells that have experienced assault can induce more effective wound healing responses to any subsequent injuries as in innate immune cells. Herein we show that wounds have a robust effect on distinct epidermal stem cells than previously thought. Of particular relevance, the first wound activated the cell adaptation program only in a specific stem cell lineage. We discovered that a specific stem cell population in that lineage produced wound memory progenitors residing in their own niche after the initial wound. These cells did not contribute to the first wound healing, but became pre-activated through priming. These wound memory cells displayed an intrinsically primed state which resulted in long term retention of reinforced migratory capacity at transcriptional and chromatin levels. This led to enhanced wound repair ability following second assault. Notably, we also found that wound memory promoted tumorigenesis through a mechanism involving the establishment of epigenetic field cancerization. Our study illuminates the major impact of wounds in epidermal stem cells and the detrimental consequences of wound memory in skin.