Fig. 1

Zone 2 hepatocytes proliferate and make a predominant contribution to homeostatic maintenance of hepatocytes throughout the liver lobule. According to their division of labor, hepatocytes in the liver tissue constitute a characteristic distribution pattern known as “liver zonation”. The present studies have collectively demonstrated that zone 2 hepatocytes exhibit the highest level of proliferative activity and are the major source of hepatocyte regeneration for homeostatic tissue turnover, as well as for tissue repair in response to certain types of injury conditions, in the entire liver lobule. Proliferation of zone 2 hepatocytes is achieved in part through the IGFBP2-mTOR-CCND1 signaling axis. In zone 3, hepatocytes that locate just adjacent to the central vein (CV) are marked by the expression of Axin2 or glutamine synthetase (GS) and self-renew, but they do not contribute to hepatocyte renewal in other regions under homeostatic conditions