GSE111500
A homeostatic Arid1a-dependent permissive chromatin state licenses hepatocyte responsiveness to liver injury-associated YAP signaling (ChIP-seq)
Following injury, differentiated epithelial cells can serve as a stem cell-independent source for tissue regeneration by undergoing reprogramming into other cell types. The intrinsic molecular basis underlying plasticity of differentiated cells remains largely unaddressed. Here we show that Arid1a, a key component of the SWI/SNF chromatin remodeling complex, controls liver regeneration and gene expression associated with emergence of injury-induced progenitor-like cells (LPLCs). Hepatocyte-specific Arid1a ablation reduces LPLC gene expression in several models of periportal liver injury and impairs liver regeneration, leading to organ dysfunction. Arid1a establishes a permissive chromatin state at LPLC-enriched genes during homeostasis, suggesting it endows hepatocytes with competence to respond to injury-induced signals.  Consistently, Arid1a facilitates binding of YAP, a critical regeneration signaling pathway, to LPLC-enriched genes, and Arid1a deletion prevents their YAP-associated induction following injury. Together, these findings provide a framework for studying the contributions of injury-induced LPLCs to periportal liver regeneration. Overall design: (i) Hepatocytes were perfused and isolated from DDC-injured mice livers, analysis of genomic occupancy of Yap in hepatocytes from DDC-injured Arid1a WT and Arid1a liver-specific KO mice by ChIP-seq (ii) Hepatocytes were perfused and isolated from normal diet feeding and DDC diet feeding mice livers, analysis of genomic occupancy of H3K27ac and H3k4me1 in hepatocytes from Arid1a WT and Arid1a liver-specific KO mice by ChIP-seq