626 Dissection of the molecular and cellular heterogeneity of dermal fibroblasts in skin fibrosis

Skin fibrosis describes an excessive accumulation of connective tissue that can manifest in association with systemic diseases such as scleroderma or locally following chronic injuries resulting hypertrophic keloid scars. This fibrotic condition is the most common and visible form fibrosis, cause severe disability, psychological stress seriously affect morbidity. So far there are no specific treatments to halt revert emphasising great unmet clinical need. Fibroblasts, major cell population tissues skin other organs, best known for their role depositing maintaining extracellular matrix. Although they were previously considered be a homogenous population, recent advances lineage tracing transcriptomic techniques have revealed astonishing functional heterogeneity between different fibroblast subpopulations skin. In homeostasis fibroblasts quiesce but rapidly “activated” during repair. While this usually transient, it becomes persistent/irreversible cancer. How pro-fibrotic phenotypes maintained long-term which subsets promoting response remain largely unknown fibrosis. Using single RNA-seq approach, we investigating changes behaviour diversity mouse model recapitulates human disease. We comparing cellular molecular early advanced lesions identify key subpopulations, regulators alterations Our findings will support development new fibroblast-targeted therapies potentially organs.