Molecular basis of transdifferentiation of pancreas to liver

C N Shen, J M W Slack, D Tosh

Research output: Contribution to journalArticle

341 Citations (Scopus)

Abstract

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 established several features of the mechanism behind this transdifferentiation. We show that a proportion of the hepatocytes arises directly from differentiated exocrine-like cells, with no intervening cell division. This conversion is associated with induction of the transcription factor C/EBP beta and the activation of differentiated hepatic products. Transfection of C/EBP beta into the cells can provoke transdifferentiation; conversely, a dominant-negative form of C/EBP beta can inhibit the process. These results indicate that C/EBP beta is a key component that distinguishes the liver and pancreatic programmes of differentiation.
Original languageEnglish
Pages (from-to)879-887
Number of pages9
JournalNature cell biology
Volume2
Issue number12
DOIs
Publication statusPublished - Dec 2000

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CCAAT-Enhancer-Binding Protein-beta
Pancreas
Liver
Hepatocytes
Organ Culture Techniques
Cell Division
Dexamethasone
Glucocorticoids
Transfection
Transcription Factors
Embryonic Structures
Pathology
Cell Line

Cite this

Molecular basis of transdifferentiation of pancreas to liver. / Shen, C N; Slack, J M W; Tosh, D.

In: Nature cell biology, Vol. 2, No. 12, 12.2000, p. 879-887.

Research output: Contribution to journalArticle

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