Probing hepatocyte heterogeneity

Abstract

To maintain homeostasis, organs replace cells lost through normal cellular turnover, often through the straightforward replication of existing cells. A recent paper in Nature shows that cells in the liver are not equivalent when it comes to their replicative capacity; rather, a subset of hepatocytes defined by the maintenance of active Wnt signaling bears the brunt of responsibility for maintaining liver mass.

Figure 1

Specialized hepatocytes in the pericentral region of the hepatic lobule. The hepatic lobule is represented as a hexagon, with blood entering through portal tracts at the periphery and converging on a central vein (CV) at the epicenter. As blood makes its way inward, it passes through three “zones” of hepatocytes. As shown by Wang et al., central vein endothelial cells release Wnt ligands, resulting in the activation of Wnt signaling in hepatocytes adjacent to the central vein (zone 3). When labeled with a Wnt-responsive reporter (illustrated in green), these cells exhibited a heightened ability to replicate, with label subsequently appearing in hepatocytes in zone 2 (and even zone 1) of the liver.