SPRR1B+ keratinocytes prime oral mucosa for rapid wound healing via STAT3 activation

Abstract Oral mucosa wounds repair faster with less scars than skin, which has been regarded as optimal wound healing system. However, the major cell subtypes that mediate mucosal fast healing remain unclear. By integrative analysis of bulk mRNA sequencing and single-cell sequencing data during wound healing in oral mucosa and skin, we identified one keratinocyte subpopulation, named SPRR1B+ keratinocytes, as major source of wound healing genes expression regulated by transcription factor STAT3. While SPRR1B+ keratinocytes were only enriched in healthy oral mucosa but not in skin, these keratinocytes were rapidly induced during skin wound healing, indicating that SPRR1B+ keratinocytes prime oral mucosa for fast wound healing. In short, by expression analysis of human oral and skin wound healing process at single-cell resolution followed by mice model validation, we identified STAT3-activated SPRR1B+ keratinocytes as the key cells priming mucosa fast repair, indicating its application in management of chronic or unhealing wounds.