Downregulation of SOCS1 increases interferon-induced ISGylation during differentiation of induced-pluripotent stem cells to hepatocytes

•ISGylation is a robust host defense response following HCV infection in hepatocytes.•Stem cells demonstrate undetectable ISGylation following interferon stimulation.•High baseline expression of SOCS1 protein negatively regulates ISGylation in stem cells.•SOCS1 gene expression is controlled through epigenetic regulation during differentiation.•Downregulating SOCS1 enhances IFN-induced ISGylation which could have implications in cancer development.