eLife Assessment
The manuscript is important in that it has the potential to advance our understanding of how liver regeneration is orchestrated after injury of pericentral hepatocytes, which are a target of many drugs and toxins. The findings are solid and suggest that midlobular hepatocytes are protected from toxin-induced injury by a genetic program delaying proliferation to prevent cell death. The effects of individual actors in the proposed program are convincingly shown but whether they act in concert and whether cell cycle arrest is indeed the protective mechanism remains to be determined.