Abstract Introduction and aims Fibroblasts, the major cell population in connective tissue, are the guardians of the extracellular matrix homeostasis. In adult tissue they exist in a quiescent state that can persist for years, but upon tissue injury, they become rapidly activated and re-enter the cell cycle, followed by deposition and reorganization of the dermal matrix. The fundamental mechanism by which fibroblasts can maintain quiescence and be primed for prompt activation is currently unknown. Deregulations of this process in the skin and other organs is associated with several pathologies including fibrosis or chronic wounds. Notably, rapid fibroblast state switching is also observed during skin development, where a tightly controlled change from a highly proliferative state to a quiescent state promotes extracellular matrix deposition and maturation of the dermal architecture. Understanding the shared mechanisms and differences between development and wound healing will help in the development of tissue regenerative therapies. Methods Using dermal development as a model for fibroblast state switching, we integrated several single-cell RNA-Seq and assay for transposase-accessible chromatin-Seq datasets of whole skin during embryonic and postnatal growth. Our novel integrated multiomics single-cell dataset can recapitulate skin developmental changes observed in vivo and reveal the major regulatory networks. Results We identified the activating protein (AP)-1 member cJun as the key regulator of fibroblast state switching in skin development and wound repair. Mechanistically, in quiescent adult fibroblasts cJun is highly transcribed, but the protein is constantly ubiquitinated and degraded, priming fibroblasts for rapid activation when needed. Upon injury cJun ubiquitination is reduced, allowing an accumulation of cJun leading to a change in AP-1 dimer composition at the chromatin level, inhibiting fibroblast quiescence and promoting proliferation and activation. Conclusions In normal wounds cJun accumulation is inhibited during the advanced (remodelling) wounding phase; however, chronic wounds and fibrotic disease conditions show a continuous and pathological cJun stabilization, which can be targeted through pharmacological intervention.