All routes lead to Rome: multifaceted origin of hepatocytes during liver regeneration

Liver is the largest internal organ that serves as the key site for various metabolic activities and maintenance of homeostasis. Liver diseases are great threats to human health. The capability of liver to regain its mass after partial hepatectomy has widely been applied in treating liver diseases either by removing the damaged part of a diseased liver in a patient or transplanting a part of healthy liver into a patient. Vast efforts have been made to study the biology of liver regeneration in different liver-damage models. Regarding the sources of hepatocytes during liver regeneration, convincing evidences have demonstrated that different liver-damage models mobilized different subtype hepatocytes in contributing to liver regeneration. Under extreme hepatocyte ablation, biliary epithelial cells can undergo dedifferentiation to liver progenitor cells (LPCs) and then LPCs differentiate to produce hepatocytes. Here we will focus on summarizing the progresses made in identifying cell types contributing to producing new hepatocytes during liver regeneration in mice and zebrafish.