Potential hepatic stem cells reside in EpCAM+ cells of normal and injured mouse liver

Abstract

Hepatic oval cells are considered to be facultative hepatic stem cells (HSCs) that differentiate into hepatocytes and cholangiocytes in severely injured liver. Hepatic oval cells have also been implicated in tumorigenesis. However, their nature and origin remain elusive. To isolate and characterize mouse oval cells, we searched for cell surface molecules expressed on oval cells and analyzed their nature at the single-cell level by flow cytometric analysis and in the in vitro colony formation assay. We demonstrate that epithelial cell adhesion molecule (EpCAM) is expressed in both mouse normal cholangiocytes and oval cells, whereas its related protein, TROP2, is expressed exclusively in oval cells, establishing TROP2 as a novel marker to distinguish oval cells from normal cholangiocytes.

FGF7 is a functional niche signal required for stimulation of adult liver progenitor cells that support liver regeneration

“…First, we examined the effect of FGF7 on LPCs in vitro. We found that a recombinant FGF7 stimulated the proliferation of HSCE1, a cell line derived from EpCAM + LPCs of adult mice (Okabe et al 2009), in a dose-dependent manner (Fig. 5A).…”

“…Among several major groups of paracrine factors, we especially focused on the FGF family because an LPC-specific marker, Trop2 (Okabe et al 2009), has previously been reported as a target gene of FGF10 in lung development (Lu et al 2005). We analyzed expression patterns of all of the paracrine Fgf ligands and found Fgf7 to be highly expressed, while we could not detect any expression of Fgf10 or Fgf3/22 belonging to the same subfamily (Supplemental Fig.…”

“…It has been well documented that stem/progenitor cell activity of a certain population of liver cells can be defined by their capacity to generate large colonies that are capable of expressing both hepatocyte and BEC lineage markers in culture (Suzuki et al 2008;Okabe et al 2009;Dorrell et al 2011;Shin et al 2011). When EpCAM + cells isolated from the FGF7 Tg mice and the control mice were subjected to in vitro colony formation assays (Okabe et al 2009), the EpCAM + cells from the Tg mice formed colonies, including those composed of >100 cells (Fig. 5I).…”

Portal fibroblasts marked by the surface antigen Thy1 contribute to fibrosis in mouse models of cholestatic liver injury

“…Traditionally, cell populations that constitute the liver have been identified and defined mainly by their morphology and anatomic location. Rigorous efforts on identifying cell specific markers, especially surface antigens, such as EpCAM for biliary epithelial cells23 and stabilin‐2 for liver sinusoidal endothelial cells,28 have enabled prospective isolation and an in‐depth analysis of liver cell populations. Nevertheless, PFs have lacked a specific cell surface antigen for selective isolation.…”

“…A single‐cell suspension from the mouse liver was obtained by a two‐step collagenase perfusion method and used for preparing hepatocytes and nonparenchymal cells (NPCs) by centrifugal separation as described 23. Aliquots of cells were blocked with anti‐Fc receptor antibody, costained with fluorescence‐conjugated and/or biotin‐conjugated antibodies (listed in Supporting Table S1) and then incubated with allophycocyanin (APC)‐conjugated streptavidin (BD Biosciences) if necessary.…”