Lineage tracing evidence for transdifferentiation of acinar to duct cells and plasticity of human pancreas

Onderzoeksoutput: Meeting abstract (Book)

92 Citaten (Scopus)

Samenvatting

Rodent studies have indicated that pancreatic exocrine acinar cells have phenotypic plasticity: they can differentiate into ductal precursors that can be converted to pancreatic ductal adenocarcinoma or insulin-producing endocrine cells. However, little is known about human acinar cell plasticity. We developed non-genetic and genetic lineage tracing methods to study the fate of human acinar cells, in culture.

Human exocrine tissue was obtained from organ donors, dissociated, and cultured. Cell proliferation and survival were measured and cell phenotypes were analyzed by immunocytochemistry. Non-genetic tracing was based on selective binding and uptake by acinar cells of a labeled lectin (UEA-1). Genetic tracing was based on adenoviral introduction of a Cre-lox reporter system, controlled by the amylase promoter.

Both tracing methods demonstrated that human acinar cells can transdifferentiate into cells that express 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 mitogen-activated protein kinase signaling.

Human acinar cells have plasticity similar to that described in rodent cells. These results might be used to develop therapeutic strategies for patients with diabetes or pancreatic cancer.
Originele taal-2English
TitelPoster presentation at BetaCell Workshop 2011: Programming beta cell development, impairment and regeneration, Helsingor, Denmark
StatusPublished - 23 okt 2011
EvenementUnknown -
Duur: 23 okt 2011 → …

Conference

ConferenceUnknown
Periode23/10/11 → …

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