Figure 1. Comparison of 2 models of liver cell homeostasis using pulse labeling.

In this hypothetical example, Sox9-expressing cells (pink) and hepatocytes (yellow) are permanently marked, as are all their progeny. (A) In the model proposed by Furuyama et al. (17), after labeling, Sox9-expressing cells differentiate into both cholangiocytes and hepatocytes, ultimately populating the entire lobule. This requires streaming of the Sox9-derived hepatocytes from zone 1 to zone 3. (B) The data presented by Malato and colleagues in this issue of the JCI (1) support a distinct model in which, under most conditions, hepatocytes are derived from other hepatocytes, without any contribution from nonhepatocytes. In some forms of injury, a small percentage of hepatocytes are derived from a nonhepatocyte cell population, perhaps from Sox9-expressing stem cells.