eLife· 2026Q1
Mid-zone hepatocytes trade proliferation for survival via Atf4-Chop axis in early acute liver injury
- 0citations
- Q1SCImago
- 2026year
Short summary
In early acute liver injury, mid-zone hepatocytes transiently suppress proliferation, prioritizing survival via the Atf4-Chop axis and the cell cycle inhibitor Btg2, to preserve regenerative capacity.
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Key points
- Mid-zone hepatocytes show transient proliferation suppression in early acute liver injury.
- This arrest is linked to acetaminophen metabolism patterns.
- The Atf4-Chop axis and Btg2 mediate the suppression of proliferation.
- This mechanism allows hepatocytes to prioritize stress adaptation over immediate proliferation.
AI-generated from the title and abstract; the full text is not read.
Abstract
Abstract Hepatocytes undergo extensive proliferation to facilitate liver repair after injury, yet early adaptive changes prior to proliferation remain unclear. Here, we report that during early acetaminophen (APAP)-induced liver injury, hepatocytes exhibit transient proliferation suppression that is most pronounced in mid-zone hepatocytes, consistent with zonal APAP metabolism. While spatial transcriptomics (ST) provided robust evidence for this arrest in the mid-zone, support for a similar arrest in pericentral hepatocytes was limited. Integrating ST with immunohistochemistry and functional studies, we identified a unique mid-zone stress-response program centered on the Atf4–Chop axis, which 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.
The authors' abstract, as published at the source. eLife, 2026 · DOI ↗
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Field: Hepatology
HepatologyMedicine