Epiplakin1 (Eppk1) marks the progenitor population in adult liver

In liver, oval cells appear in the portal area in response to injury and are considered as transit amplifying cells. The current understanding is that these cells play a role in the maintenance of the homeostasis of liver upon injury by their potential to give rise to both the hepatocytes and cholangiocytes, which is similar to the hepatoblasts that are known as embryonic hepatic progenitor cells. However, their exact role and origin remain unclear. Lineage tracing study is considered as a powerful tool to identify the stem cells or progenitor cells. We search for useful markers to identify oval cells and trace their progenies. We have previously reported that Eppk1, a plakin family gene known as a cytolinker protein, marks the pancreatic stem/progenitor cells (Yoshida T et al., 2008 ). We showed that at E8.5 Eppk1 is expressed in the foregut endoderm, which gives rise to the endoderm organs, such as pancreas and liver (Yoshida T et al., 2009). To test whether Eppk1 is a useful marker for stem / progenitor cells in the liver, we analyzed the expression patterns of Eppk1. We found that Eppk1 marks oval cell populations in the adult injured liver. In the developing embryos, Eppk1 expression was observed in the cholangiocyte progenitor population. After birth, in normal and injured adult liver, Eppk1 expression was observed in the cholangiocytes and oval cells, respectively. Taken together, these results indicate that Eppk1 is a useful marker to identify oval cells.