bipotential hepatic progenitor cells in the developing Intermediate filament proteins have been reported to human liver. (HEPATOLOGY 1996;23:476-481.) be expressed in a cell lineage-specific manner during morphogenesis. We studied the expression of cytokeratin (CK) 14, CK19, and vimentin and of the hepatocyte-Extensive evidence suggests that several intermedispecific HepPar1 antigen during the development of huate filament proteins are expressed in a cell lineageman liver. Nineteen fetal livers (gestational ages 4 to 40 specific manner during morphogenesis and regeneraweeks), 3 normal infant livers, and 3 normal adult livers tion. 1,2 Cytokeratin (CK)14, which distinguishes stratiwere studied by immunoperoxidase staining of paraffin fying epithelial cell types from simple epithelial cell sections with monoclonal anti-CK19, anti-vimentin, and
types, 1,3 has been detected in cultured liver epithelial HepPar1 antibodies and polyclonal anti-CK14 antibodies. Double-immunostaining for CK14 and CK19 as well cells derived from developing rat liver. 4,5 CK19, which as bile duct cytokeratin and HepPar1 antigen was also is found in a large number of epithelial cell types, 6 has done. CK19 and HepPar1 antigen were the first markers been used as a marker for biliary epithelial cells. 7,8 detected in immature progenitor cells of the liver pri-In addition, CK19 was localized in oval cells, which mordium at 4 weeks' gestation. During subsequent liver proliferate during liver regeneration and carcinogenedevelopment, the progenitor cells expressed HepPar1 sis in rodents. [9][10][11] Vimentin, which represents an interantigen, CK14, and CK19, from 8 to 14 weeks' gestation. mediate filament protein of mesenchymal cells, was As hepatocyte differentiation progressed, expression of reported to be expressed during differentiation of im-HepPar1 antigen increased, and CK14 and CK19 were mature cells into epithelial cells of kidney, ovary, and abrogated from hepatoblasts at 14 to 16 weeks' gestation.
testis. 12 Finally, a monoclonal antibody that specifically In contrast, as progenitor cells transformed into ductal plate cells, CK19 expression increased and persisted in reacts with hepatocytes (HepPar1) has recently been differentiated bile ducts, whereas CK14 and HepPar1 developed. 13 The expression of these proteins during antigen were lost. Vimentin was detected in ductal plate human liver development, however, has not been studand biliary epithelial cells from 9 to 36 weeks' gestation, ied in detail.
but not in hepatoblasts or hepatocytes. Double-immunothe ductal plate cells, which differentiate along the biliary epithelial cell lineage. [14][15][16] To evaluate cell lineage-Abbreviation: CK, cytokeratin; Ig, immunoglobulin. specific markers during liver morphogenesis, we inves-From the