Dynamic epigenetic and transcriptional changes drive cellular plasticity in the liver

Following liver injury, a subset of hepatocytes adopt features of biliary epithelial cells (BECs) in a process known as biliary reprogramming. The aim of this study is to elucidate the molecular events accompanying this dramatic shift in cellular identity. We treated RosaYFP mice (injected with AAV8-TBG-Cre to lineage label hepatocytes) with DDC to induce hepatocyte-to-biliary reprogramming, then isolated Cd45-/Cd31-/Cd11b- living cells by flow sorting. Samples were either sorted from remaining cells (bulk), which include YFP+ and YFP- cells, or by sorting for YFP+ lineage-labeled hepatocyte-derived cells (YFP). In addition, we examined the role of TGF? signaling by profiling cells undergoing reprogramming in mice with hepatocyte-specific deletion in the downstream TGF? signaling component Smad4.