{
  "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_shown": true,
  "affiliations": [
    "Yunnan Key Laboratory of Cell Metabolism and Diseases, Center for Life Sciences, School of Life Sciences, Yunnan University, Kunming, China."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 9,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Yaying Zhu"
    },
    {
      "affs": [
        0
      ],
      "name": "Chengxiang Deng"
    },
    {
      "affs": [
        0
      ],
      "name": "Bo Chen"
    },
    {
      "affs": [
        0
      ],
      "name": "Jia He"
    },
    {
      "affs": [
        0
      ],
      "name": "Yanan Liu"
    },
    {
      "affs": [
        0
      ],
      "name": "Shan Lei"
    },
    {
      "affs": [
        0
      ],
      "name": "Weiju Lu"
    },
    {
      "affs": [
        0
      ],
      "name": "Cheng Peng",
      "orcid": "0000-0002-0448-0094"
    },
    {
      "affs": [
        0
      ],
      "name": "Zhao Shan",
      "orcid": "0000-0001-5064-1023"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/b8kjkmrt1txvp.bib",
  "cited_by": 0,
  "doi": "10.7554/elife.108646",
  "fulltext_url": "https://europepmc.org/articles/PMC13707374",
  "id": "b8kjkmrt1txvp",
  "issns": [
    "2050-084X"
  ],
  "landing_url": "https://europepmc.org/article/MED/42929492",
  "language": "eng",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "2721|Liver physiology and pathology"
    ]
  ],
  "openalex": "W4415282991",
  "pdf_url": "https://europepmc.org/articles/PMC13707374?pdf=render",
  "pmcid": "PMC13707374",
  "pmid": "42929492",
  "published": "2026-10-26",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/b8kjkmrt1txvp.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:22:01Z",
      "native_id": "MED:42929492",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42929492"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2721|Liver physiology and pathology",
      "subfield": "general"
    }
  ],
  "title": "Mid-zone hepatocytes trade proliferation for survival via Atf4-Chop axis in early acute liver injury.",
  "title_text": "Mid-zone hepatocytes trade proliferation for survival via Atf4-Chop axis in early acute liver injury.",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:22:01Z",
  "url": "https://research.draconitic.com/paper/b8kjkmrt1txvp",
  "venue": "ELife",
  "versions": []
}