Expression of nestin-green fluorescent protein transgene marks oval cells in the adult liver

Oval cells, which become apparent in the liver after chronic injury, serve as bipotent progenitors for differentiated hepatocytes and cholangiocytes. We found that, in the liver of adult transgenic mice in which expression of green fluorescent protein (GFP) is driven by regulatory elements of the nestin gene, the GFP signal marks a subpopulation of small epithelial cells that meet the criteria for oval cells, including morphology, localization, antigenic profile, and reactivity in response to injury. In the regenerating and developing liver, we also found nestin-GFP-positive cells that express hepatocyte markers; such cells may correspond to transiently appearing differentiating progeny of oval cells. During development, GFP-expressing cells in the liver emerge relatively late, after the appearance of differentiated hepatocytes and cholangiocytes. Our results suggest that nestin-GFP cells in the liver correspond to a specialized cell type whose primary function may be to serve as a reserve for adult liver epithelial cell types.