Single cell analysis of switch-like induction of XXXX in liver cell lines.

@entity7772 @entity22038 @entity19 @entity35 @entity157
The shape of the dose-response curve may vary depending on whether one examines response at a population or a single cell level. Populations of cells may exhibit a graded response whereas single cell responses may have threshold or switch-like behavior. Studies in vivo and in vitro using primary hepatocyte cultures have shown that induction of @entity7772 in the liver exhibits switch-like behavior in response to @entity22038 ( @entity22038 ). The goal of the present study was to determine if two liver cell lines (H4IIE @entity35 @entity157 and Hepa 1c1c7 @entity19 @entity157 ) also show switch-like behavior and develop experimental models for studying mechanisms of these switch-like responses. Both cell lines were analyzed via concentration-response and time-course studies using quantitative real-time PCR, revealing a sigmoidal concentration-response curve for @entity7772 mRNA induction at the population level. To study @entity7772 protein induction on a single cell level, flow cytometry was employed. In both cell lines the distribution of fluorescence increased with increasing concentrations of @entity22038 . The switch behavior was more pronounced in the H4IIE cells than in the Hepa 1c1c7 cells, exhibiting a well-defined shift of induction from the "off" to the "on" state. The concentration-response curve at the single cell level appeared more switch-like with two populations of cells-basal levels and maximally induced. Immunocytochemistry studies of individual cells also support these conclusions. Our data support the hypothesis that @entity22038 induces @entity7772 in a switch-like fashion in H4IIE @entity35 @entity157 cells. These cells can now be used to study the mechanism of the biological switch.
