Cell-cell interaction can influence drug-induced differentiation of @entity19 XXXX cells.

@entity4998 @entity19 @entity189 @entity3733 @entity1968
When cultured in the presence of either @entity1968 (RA) or @entity3733 ( @entity3733 ), aggregates of the P19 line of @entity19 @entity189 ( @entity189 ) cells differentiate and the spectrum of cell types formed depends on the drug dose. It is shown here the @entity189 cells rapidly lose their colony-forming ability when cultured as aggregates in the presence of @entity3733 . This loss of plating efficiency (PE) also occurs rapidly following RA treatment. Loss of PE has been used as a quantitative procedure for assessing the rate of drug-induced differentiation. The relationship between drug dose and loss of PE is much steeper for @entity3733 than for RA, suggesting that these two drugs affect different stages of the differentiation decision-making apparatus. Mutant @entity189 cell lines (D3 and RAC65) do not differentiate in the presence of drug-inducers ( @entity3733 and RA, respectively). Neither @entity4998 mutant has an altered ability to form gap junctions. When D3 and P19 cells were mixed within the same @entity3733 -treated aggregates, the D3 cells remained undifferentiated and the P19 cells differentiated much less efficiently than if they were cultured in the absence of the D3 cells. When RAC65 and P19 cells were mixed in RA-treated aggregates, each cell responded to the drug as though the other were absent. Thus RA behaves as a cell-autonomous inducer of differentiation, whereas @entity3733 -induced differentiation seems to be mediated by interactions between neighboring cells.
