In vivo reprogramming of wound-resident cells generates skin epithelial tissue.

Large cutaneous ulcers are, in severe cases, life threatening1,2 . As the global population ages, non-healing ulcers are becoming increasingly common1,2 . Treatment currently requires the transplantation of pre-existing epithelial components, such as skin grafts, or therapy using cultured cells2 . Here we develop alternative supplies of epidermal coverage for the treatment of these kinds of wounds. We generated expandable epithelial tissues using in vivo reprogramming of wound-resident mesenchymal cells. Transduction of four transcription factors that specify the skin-cell lineage enabled efficient and rapid de novo epithelialization from the surface of cutaneous ulcers in mice. Our findings may provide a new therapeutic avenue for treating skin wounds and could be extended to other disease situations in which tissue homeostasis and repair are impaired.