The mammalian liver has remarkable regenerative capacities, but whether adult hepatic stem cells (HepSCs) exist is debated. Now, on , Minoru Tanaka and colleagues identify a cell-surface marker for mouse liver oval cells (OCs) and show that isolated OCs contain potential HepSCs. Liver regeneration generally does not require stem cells; instead, hepatocytes,which perform most of the liver's metabolic functions, proliferate. Blocking injury-induced hepatocyte proliferation, however, leads to the proliferation of OCs (facultative progenitor cells that probably generate both hepatocytes and cholangiocytes, the bile-duct-forming liver cells). The authors find that the adhesion molecule EpCAM is expressed in both OCs and cholangioblasts,whereas the EpCAM-related protein TROP2 is only present in injury-activated OCs. EpCAM-positive cells isolated from either injured or normal liver form colonies in vitro, and these clonally expanded cells can differentiate into hepatocytes and cholangiocytes, indicating that the EpCAM-positive cell population contains potential HepSCs. Future research will show whether these potential HepSCs can self-renew and repopulate the liver in vivo.
