Laser-induced skin microenvironment remodeling via exosomal CEBPA-mediated crosstalk between keratinocyte and fibroblast.

Laser treatments are widely applied in aesthetic and clinical dermatology to promote skin rejuvenation by inducing controlled tissue disruption, activating repair processes involving keratinocyte proliferation, fibroblast migration, and extracellular matrix remodeling. However, the cellular specialization and intercellular communication mechanisms, particularly in the early stages following laser treatment, remain poorly understood. Using single-cell RNA sequencing, we analyzed laser-treated and untreated skin, revealing significant differences in cell populations and functions. Keratinocytes and fibroblasts displayed the most prominent shifts in cell number and transcriptional diversity following laser exposure. In early-stage laser-induced skin remodeling, distinct keratinocyte subpopulations actively orchestrated skin repair, immune responses, and regenerative signaling. Cell-cell communication analysis uncovered a dynamic crosstalk between keratinocytes and fibroblasts. Functional validation through co-culture revealed this crosstalk was mediated by exosomes derived from laser-treated keratinocytes, which were enriched with CEBPA. Mechanistically, these exosomes enhanced keratinocyte proliferation through YAP/TAZ activation, while concurrently suppressing fibroblast activity by upregulating IGFBP3 expression during the early phase of laser-induced skin remodeling. Our findings provide new insights into how laser treatments modulate cellular behavior and intercellular signaling, emphasizing the therapeutic potential of exosome-based strategies for promoting skin regeneration and rejuvenation.