The appearance of hepatic foci in the pancreas has been described in animal
experiments and in human pathology. Here we show that pancreatic cells can
be converted into hepatocytes by treatment with a synthetic glucocorticoid
, dexamethasone. This occurs both in a pancreatic cell line, AR42J-B13, and
in organ cultures of pancreatic buds from mouse embryos. We have establish
ed several features of the mechanism behind this transdifferentiation. We s
how that a proportion of the hepatocytes arises directly from differentiate
d exocrine-like cells, with no intervening cell division. This conversion i
s associated with induction of the transcription factor C/EBP beta and the
activation of differentiated hepatic products. Transfection of C/EBP beta i
nto the cells can provoke transdifferentiation; conversely, a dominant-nega
tive form of C/EBP beta can inhibit the process. These results indicate tha
t C/EBP beta is a key component that distinguishes the liver and pancreatic
programmes of differentiation.