Fibroblasts, the major cell population in connective tissues, are best known for their role in depositing and maintaining extracellular matrix. In homeostasis most fibroblasts quiesce, but are rapidly “activated” during tissue repair. While this is usually transient, it becomes persistent/irreversible in fibrotic diseases and cancer. We will explore the transcriptional and epigenetic changes inhibiting resolution of pathological fibroblast behaviours. Using physiologically relevant 3D-cultures we will screen fibroblasts from normal and diseased skin for intrinsically maintained pro-fibrotic phenotypes and dissect the epigenetic and transcriptional regulators by combining ATAC-seq and RNA-seq. Identified candidates will be functionally validated and evaluated for therapeutic applications.
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