Plasticity of human pancreas: transdifferentiation of acinar to duct cells

Onderzoeksoutput: Meeting abstract (Book)

Samenvatting

Acinar cells, being the largest cell population of the pancreas, are an attractive source for generating beta cells for cell replacement in diabetes. In rodents, acinar cells can differentiate to insulin-producing cells. The plasticity of rodent acinar cells raises the question if human acinar cells have the same capacity. Not much is known about the plasticity of human acinar cells. Therefore, genetic and non-genetic lineage tracing methods were developed to study the fate of human acinar cells in culture.
Human exocrine cells, obtained from organ donors, were dissociated and put in culture. Non-genetic lineage tracing was based on selective binding and uptake of the lectin Ulex europaeus agglutinin 1 by acinar cells. Within 1 week of culture, the percentage of ductal cells that contained the lectin increased from 1% to nearly 18%. These cells expressed specific ductal markers, such as CK19, HNF1B, SOX9, CD133, CAII, CFTR. Acinar cells have the capacity to transdifferentiate to cells with a ductal phenotype. This conclusion was confirmed by genetic lineage tracing, which was based on adenoviral introduction of a Cre-lox reporter system, controlled by the amylase promoter.
Analysis of different signalling pathways showed that transdifferentiation was decreased by inhibiting mitogen-acitvated protein kinase signalling.
The observation of human acinoductal transdifferentiation offeres hope to exploit this plasticity for clinical applications.
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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