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

Article · Zhu Y, Deng C, Chen B, He J, Liu Y, Lei S, Lu W, Peng C, Shan Z

- Archive id: doi:10.7554/elife.108646
- Published: 2026-10-26
- Venue: eLife
- DOI: https://doi.org/10.7554/elife.108646
- PMID: 42929492
- PMCID: PMC13707374
- Citations: 0
- Source URL: https://doi.org/10.7554/elife.108646
- PDF: https://europepmc.org/articles/PMC13707374/pdf
- Provenance: europepmc

## 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 reproduced under CC-BY (article license as recorded by Europe PMC; abstract reproduced unmodified apart from markup removal)._

Topics: [Single-Cell & Spatial Omics](https://space-kitty.com/topics/single-cell-spatial)

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