SPECIALIZATION SWITCH IN DIFFERENTIATING EMBRYONIC RAT-LIVER PROGENITOR CELLS IN RESPONSE TO SODIUM-BUTYRATE

Embryonic (E) 12 rat liver epithelial cells constitute a population of bipotential progenitor cells which can differentiate along the hepatocyte (Hep) or biliary epithelial cell (BEG) lineage in primary culture. In the present study, E12 cells were seeded on fibronectin-coated substratum and exposed to sodium butyrate (SE) for various exposure times, and the emergence of the Rep or BEC phenotype was monitored by following the variations in albumin production and assessing the appearance of the two surface-exposed markers HES(6) and BDS7. Continuous exposure to SE resulted into a major reduction in albumin production and, at Day 9 postseeding, few cells coexpressed BDS, and albumin. When cells were exposed to SE for 5 days and then cultured for an additional 5 days without SB, they massively express BDS7, but very little HES(6). Moreover, the reverse sequence, i.e., 5 days without SE followed by 5 days with it, led to the appearance of many cells expressing both HES(6) and BDS7. These results indicate that progenitors committed preferentially along the Hep lineage still have the option to switch to BECs, at a transitional stage that we refer to as a ''differentiation window.'' (C) 1995 Academic Press, Inc.