Mid-zone hepatocytes trade proliferation for survival via Atf4-Chop axis in early acute liver injury.
- 1Yunnan Key Laboratory of Cell Metabolism and Diseases, Center for Life Sciences, School of Life Sciences, Yunnan University, Kunming, China.
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.
Related
- Pitch Metrics and the Trade-Offs Between Elbow Injury and Performance in Major League Baseball Pitchers
- Real-world device survival, revision burden and observed pain patterns after epidural spinal cord stimulation for neuropathic pain in adults with spinal cord injury: protocol for a longitudinal observational cohort study using routine clinical data
- Silver spoon effect: early-life environment and adult survival in a primate.
- Epigenetic age acceleration enhances prediction of overall survival in early-stage non-small cell lung cancer
- Early Prognostic Value of the Freiburg Index of Post-Transjugular Intrahepatic Portosystemic Shunt Survival in Patients With Hepatocellular Carcinoma Undergoing Liver Transplantation
BibTeX
@article{zhu2026midzone,
title = {{Mid-zone hepatocytes trade proliferation for survival via Atf4-Chop axis in early acute liver injury.}},
author = {Yaying Zhu and Chengxiang Deng and Bo Chen and Jia He and Yanan Liu and Shan Lei and Weiju Lu and Cheng Peng and Zhao Shan},
journal = {ELife},
year = {2026},
month = oct,
doi = {10.7554/elife.108646},
url = {https://europepmc.org/article/MED/42929492},
note = {CC BY},
}
RIS
TY - JOUR
TI - Mid-zone hepatocytes trade proliferation for survival via Atf4-Chop axis in early acute liver injury.
AU - Yaying Zhu
AU - Chengxiang Deng
AU - Bo Chen
AU - Jia He
AU - Yanan Liu
AU - Shan Lei
AU - Weiju Lu
AU - Cheng Peng
AU - Zhao Shan
PY - 2026
DA - 2026/10/26
JO - ELife
DO - 10.7554/elife.108646
UR - https://europepmc.org/article/MED/42929492
AB - 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.
SN - 2050-084X
ER -