A role for ETV1 and endothelial cell-derived extracellular vesicle microRNAs in priming fibroblast response to vesicle-bound FGF2
Communication between various cell types following wounding is paramount for proper healing and regeneration of injured tissue. Endothelial cells and fibroblasts are critical cellular players involved in cutaneous wound repair, yet their communication mechanisms are not well understood. It has previously been shown that extracellular vesicles derived from endothelial cells (ECEVs) induce dermal fibroblasts to express a gene signature correlated with FGF2-mediated cancer associated fibroblast (CAF) activation, under the control of transcription factor ETV1. In this report, we utilize loss-of-function studies to define the mechanistic role of ETV1 in conferring this ECEV-induced transcriptomic shift and functional change in fibroblasts. Additionally, we identify highly expressed ECEV microRNAs and examine their potential contribution to the ECEV mechanism through downstream gene modulation. In summary, we describe a plausible mechanism by which both ETV1 and top ECEV microRNAs promote a genotypic and phenotypic shift in dermal fibroblasts that have taken up ECEVs. Overall design: Small RNA sequencing of extracellular vesicles isolated from primary human dermal microvascular endothelial cells (ECEVs) using a PEG-based isolation reagent.