Mid-zone hepatocytes trade proliferation for survival via Atf4-Chop axis in early acute liver injury.

In a mouse model of acetaminophen (APAP)-induced acute liver injury, mid-zone hepatocytes show transient proliferation suppression linked to zonal metabolism and a stress-response program.

• Why it matters: Early adaptive changes before hepatocyte proliferation are unclear, limiting understanding of how liver repair is coordinated immediately after injury.
• What they did: Using spatial transcriptomics plus Cut&Run, immunohistochemistry, and functional studies, the study identified an Atf4-Chop–centered mid-zone stress program and tested its downstream target Btg2.
• The result: The Atf4-Chop axis suppresses proliferation via the cell-cycle inhibitor Btg2, supporting a model where mid-zone hepatocytes prioritize stress adaptation to preserve regenerative capacity for later repair.