Molecular Characterization of Cultured Adult Human Liver Progenitor Cells

Hepatic progenitor cells hold great promise as a self-renewing cell source for cell-based regenerative therapies as well as in vitro pharmacological testing. There is a fundamental need to identify and characterize these cells with respect to discriminative marker genes especially those encoding cell surface proteins, which can be utilized for the identification and isolation of these progenitor cells. In this study, comparative global gene expression profiling was performed with two epithelial cell types isolated from human livers that showed progenitor characteristics (type 1 and 2 cells), two human embryonic stem cell lines H1 and H9, and with primary human hepatocytes. The analysis revealed that the transcriptome of type 1 cells is more similar to that of human embryonic stem cells than to that of human hepatocytes. Among the list of genes expressed in type 1 cells are cadherins (CDH3), tight junction proteins (CLDN4), receptors (DDR1), integrins (ITGB4), cell adhesion molecules (EpCAM/TACSTD1), cell surface proteins (CD133/PROM1, ANXA3, and CD24), and a gene encoding the multidrug resistance protein MRP4/ABCC4. Finally, we were able to localize type 1 progenitor cells in Canals of Hering and in cells of ductular reactions within sections of normal and diseased human liver using ANXA3 and CLDN4 antibodies. Our study confirms the progenitor identity of type 1 cells and identifies novel markers that could be used for further studies on their characteristics and isolation using marker-based cell sorting strategies.