摘要：SummaryKeratinocyte differentiation is an intricate process that is regulated by multiple mediators. Using cultured human keratinocytes, we found that lysophosphatidic acid (LPA) induced the differentiation of a previously unsuspected keratinocyte subpopulation expressing the extracellular matrix protein, thrombospondin-1 (THBS1). This action of LPA was mediated by the RHO/ROCK-SRF signaling downstream of LPA1and LPA5receptors and required ERK activity. Suppression of THBS1in vitrosuggested a migratory role of THBS1+keratinocytes. Moreover, we analyzed publicly deposited single-cell RNA sequencing dataset and identifiedThbs1-expressing keratinocytes in the mouse wound skin. Immunohistochemistry analysis revealed that Thbs1+keratinocytes were apparently differentiated from basal keratinocytes upon wounding, subsequently polarized and migrated suprabasally toward the wound front, and eventually underwent terminal differentiation in the neo-epidermis. Importantly, inhibition of Erk activity suppressed Thbs1+keratinocyte differentiation in wound healing. Based on these findings, we suggest that THBS1+keratinocyte is a migratory keratinocyte subpopulation that facilitates epidermal wound healing.Graphical abstractDisplay OmittedHighlights•Single-cell RNA sequencing reveals a keratinocyte subpopulation expressing THBS1•LPA and ERK activity are required for the induction of THBS1+keratinocyte•Thbs1+keratinocytes are differentiated from basal keratinocytes upon epidermal wounding•Thbs1+keratinocytes are migratory cells and may contribute to epidermal wound healingBiological sciences; Cell biology; Stem cells research
