Single-nucleus chromatin landscapes of cholestatic injury and repair in mice liver

Hepatocyte reprogramming is essential for liver regeneration, yet its epigenetic mechanisms remain poorly understood. Using single-nucleus ATAC-seq, we profiled chromatin accessibility in a mouse model of diet-induced cholestasis at six time points: healthy (D0), injury (D8, D17), and recovery (R2, R7, R21). We analyzed 75,452 high-quality nuclei, identifying 15 liver cell types, including reprogrammed hepatocytes called LPLCs. Among 221,845 accessible chromatin regions, 192,079 showed differential accessibility. LPLCs exhibited enriched binding motifs for SWI/SNF (SMARCC1) and AP-1 (FOS, JUND and JUNB) complexes, highlighting their roles in transcriptional regulation. This study provides a comprehensive chromatin accessibility landscape of liver injury and regeneration, suggesting SWI/SNF and AP-1 as potential therapeutic targets.