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Significance Liver has a remarkable regenerative capacity following injuries. However, the cellular dynamics of how hepatocytes are replenished during homeostasis and upon liver injuries remains largely unclear. By using genetic lineage tracing strategies on rare Lgr5+ hepatocytes surrounding the central veins of the liver lobule, this study shows that Lgr5+ hepatocytes are self-maintained during normal homeostasis and various liver injuries, and contributed to hepatocarcinogesis in two different hepatocellular carcinoma (HCC) models. Our findings provide an insight on hepatocyte regeneration under homeostasis and liver injuries and uncover Lgr5+ hepatocytes as potential cellular origin in HCC development.

Lgr5 + pericentral hepatocytes are self-maintained in normal liver regeneration and susceptible to hepatocarcinogenesis

Lgr5 ⁺ pericentral hepatocytes are self-maintained in normal liver regeneration and susceptible to hepatocarcinogenesis