{"id":"doi:10.7554/elife.108646","kind":"article","title":"Mid-zone hepatocytes trade proliferation for survival via Atf4-Chop axis in early acute liver injury","authors":["Zhu Y","Deng C","Chen B","He J","Liu Y","Lei S","Lu W","Peng C","Shan Z"],"author_count":9,"year":2026,"published":"2026-10-26","venue":"eLife","cited_by":0,"doi":"10.7554/elife.108646","arxiv_id":null,"nct_id":null,"source_url":"https://doi.org/10.7554/elife.108646","archive_url":"https://space-kitty.com/papers/doi:10.7554/elife.108646","updated":null,"pmid":"42929492","pmcid":"PMC13707374","openalex_id":null,"pdf_url":"https://europepmc.org/articles/PMC13707374/pdf","abstract":"Hepatocytes undergo extensive proliferation to facilitate liver repair after injury, yet early adaptive changes prior to proliferation remain unclear. Using a mouse model of acetaminophen (APAP)-induced liver injury, we show that hepatocytes undergo transient proliferation suppression that is most pronounced in mid-zone hepatocytes, consistent with zonal APAP metabolism. Although spatial transcriptomics (ST) alone could not independently confirm zonal proliferative restraint, ST analysis identified a unique mid-zone stress-response program centered on the Atf4-Chop axis. By integrating Cut&Run with immunohistochemistry and functional studies, we found that the Atf4-Chop axis suppresses proliferation via the cell-cycle inhibitor Btg2. Together, our findings support a model in which mid-zone hepatocytes transiently prioritize stress adaptation over proliferation, thereby preserving regenerative capacity for subsequent liver repair.","abstract_license":"CC-BY (article license as recorded by Europe PMC; abstract reproduced unmodified apart from markup removal)","license":"CC-BY","is_open_access":true,"retracted":false,"peer_reviewed":null,"categories":[],"details":null,"provenance":"europepmc","attribution":"Abstract of \"Mid-zone hepatocytes trade proliferation for survival via Atf4-Chop axis in early acute liver injury\" by Zhu Y, Deng C, Chen B et al., https://doi.org/10.7554/elife.108646, used under its Creative Commons Attribution license (CC-BY); markup removed, otherwise unmodified.","topics":[{"slug":"single-cell-spatial","name":"Single-Cell & Spatial Omics","domain_slug":"biotech"}],"cited_in_dossiers":[]}