FXR isoform selective transcriptional activation in mouse liver organoids

The farnesoid X receptor (FXR) is a nuclear receptor activated by bile acids that regulates metabolic processes. FXR is expressed as four isoforms (a1-4), and their relative abundance is specific to tissue and bio-energetic conditions (Correia JC et al. 2015). Depending on the FXR isoform expressed, there is a degree of selectivity in target-genes activation. In this dataset, we defined FXR-isoforms selective effects on transcription in mouse liver organoids after treatment with the FXR agonist Obeticholic acid(OCA). By linking the DNA binding profiles of the FXR isoforms with their transcriptional output, we concluded that differential DNA binding plays a defining role in FXR-isoform target gene selectivity. Overall design: FXR -/- mouse liver organoids were transduced with mouse FXR isoforms a1, a2, a3, a4 or H2b-NeonGreen(ko) using lentiviral vectors (pLV IRES PuroR). After selection, the organoids were differentiated into the hepatocyte lineage before treatment with OCA