Generation of keratinocyte stem-like cells from human fibroblasts via a direct reprogramming approach.

Skin repair and reconstruction are important after severe wound and trauma. Keratinocyte stem cells (KSCs) in the basal layer of the epidermis can regrow the stratified epidermis but are almost depleted after skin injury. Thus, generating enough KSCs is indispensable for skin regeneration. Pluripotent stem cells such as ESC and iPSC can differentiate into KSCs, but their applications are challenged by ethical issues and risks of tumor formation. Lineage reprogramming from one cell type into another one makes it feasible to generate the desired cell type. Here, we develop a method to convert human fibroblasts into induced keratinocyte stem-like cells (iKSC) by coupling transient expression of reprogramming factors with a chemically defined culture medium, without the formation of iPSC. iKSC resemble normal KSC in the morphological and phenotypic features and can differentiate in vitro and regenerate stratified epidermis after transplantation in vivo. Therefore, iKSC may provide abundant cellular sources for skin repair and regeneration.