Liver cells buy recovery capacity by briefly stopping division in mice
After liver injury, such as from a paracetamol overdose, liver cells need to regenerate quickly. But some cells first stop dividing altogether. New research in mice shows this is not a failure but a protective mechanism.
The liver is divided into zones. The middle zone (zone 2) is the primary source of new liver cells during repair. In mice given a high dose of paracetamol (acetaminophen), researchers observed that cells in exactly this zone suddenly slowed their division. This was paradoxical: the cell most needed for repair temporarily stops growing.
Stress response as a survival strategy
The researchers combined spatial transcriptomics (a method that measures gene activity at specific locations in tissue) with functional studies. They found that mid-zone liver cells activate a specific stress response via a signalling axis called Atf4-Chop. This in turn activates a cell-division inhibitor, Btg2.
The result: cells temporarily slow their division to manage stress. After 24 hours, division gradually resumed. According to the researchers, a cell that pauses this way preserves its capacity to regenerate effectively later. A cell that divides too early while under stress is more likely to die.
Relevant for liver injury and drug safety
Paracetamol overdose is the leading cause of acute drug-induced liver failure worldwide. This mechanism may help explain why some cells survive the initial wave of damage while others do not. The study appeared in the journal eLife. These are mouse experiments; whether this mechanism works identically in humans was not established in this study.
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