Lineage tracing evidence for in vitro acinar to duct cell transdifferentiation in human pancreas

Research output: Chapter in Book/Report/Conference proceedingMeeting abstract (Book)

Abstract

Background and aims: It is becoming increasingly clear from animal studies that pancreatic exocrine acinar cells exhibit phenotypic plasticity. In rodents, acinar cells can differentiate into ductal precursors, that can convert into pancreatic ductal adenocarcinoma or insulin-producing endocrine cells. However, little is known about acinar cell plasticity in human cells. We developed non-genetic and genetic lineage tracing methods to study the fate of human acinar cells in culture.
Methods: Human exocrine tissue obtained from organ donors was dissociated and put in culture. Cell proliferation and survival was examined, and cellular phenotype was analyzed by immunocytochemistry. Non-genetic tracing was based on selective binding and uptake of a labeled lectin (UEA-1) by acinar cells. Genetic tracing was based on adenoviral introduction of a Cre-lox reporter system driven by the amylase promoter.
Results: Both tracing methods demonstrate that human acinar cells have the inherent capacity to transdifferentiate into cells expressing specific ductal markers such as CK19, HNF1B, SOX9, CD133, CAII and CFTR. Within one week of culture, all surviving acinar cells had acquired a ductal phenotype. This transdifferentiation was decreased by inhibiting MAPK signaling.
Conclusions: Human acinar cells have a similar plasticity as was previously demonstrated in rodents. These results may have important consequences for developing therapeutic strategies in diabetes and pancreatic cancer.
Original languageEnglish
Title of host publicationPoster presentation PhD Day - Research Unlimited Brussels 2011
Publication statusPublished - 5 Apr 2011

Keywords

  • lineage tracing
  • transdifferentiation
  • acinar
  • duct
  • human
  • lectin
  • adenoviral vector
  • cre/lox

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