Journal
SCIENCE ADVANCES
Volume 9, Issue 35, Pages -Publisher
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/sciadv.adh1168
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This study provides important insights into the cellular response to extracellular vesicles (EVs), showing that EV dose has a more significant effect than cell source. At high doses, exocytosis is down-regulated and lysosomal activity is up-regulated. However, at low doses, specific responses based on EV cell source are observed, reflecting the activities of the EV's source cells. Furthermore, immune cell-derived EVs are most associated with recipient cells.
Extracellular vesicles (EVs) have been established to play important roles in cell-cell communication and shown promise as therapeutic agents. However, we still lack a basic understanding of how cells respond upon exposure to EVs from different cell sources at various doses. Thus, we treated fibroblasts with EVs from 12 different cell sources at doses between 20 and 200,000 per cell, analyzed their transcriptional effects, and functionally confirmed the findings in various cell types in vitro, and in vivo using single-cell RNA sequencing. Unbiased global analysis revealed EV dose to have a more significant effect than cell source, such that high doses down-regulated exocytosis and up-regulated lysosomal activity. However, EV cell source-specific responses were observed at low doses, and these reflected the activities of the EV's source cells. Last, we assessed EV-derived transcript abundance and found that immune cell-derived EVs were most associated with recipient cells. Together, this study provides important insights into the cellular response to EVs.
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