Potential hepatic stem cells reside in EpCAM+ cells of normal and injured mouse liver
2009
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. EpCAM + cells
isolated from injured liver proliferate to form colonies in vitro, and the
clonally expanded cells differentiate into hepatocytes and cholangiocytes,
suggesting that the oval cell fraction contains potential HSCs. Interestingly,
such cells with HSC characteristics exist among EpCAM + cells of
normal liver. Intriguingly, comparison of the colony formation of
EpCAM + cells in normal and injured liver reveals little difference
in the number of potential HSCs, strongly suggesting that most proliferating
mouse oval cells represent transit-amplifying cells rather than HSCs.
Keywords:
- Correction
- Source
- Cite
- Save
- Machine Reading By IdeaReader
76
References
234
Citations
NaN
KQI