Adult human pancreatic acinar cells dedifferentiate into an embryonic progenitor-like state in 3D suspension culture

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Samenvatting

Human pancreatic exocrine cells were cultured in 3D suspension and formed pancreatospheres composed of acinar-derived and duct-like cells. We investigated, up to 6 days, the fate of human pancreatic acinar cells using uorescein-conjugated Ulex Europaeus Agglutinin 1 lectin, a previously published acinar-specific non-genetic lineage tracing strategy. At day 4, fluorescence-activated cell sort for the intracellularly incorporated FITC-conjugated UEA1 lectin and the duct-speci c CA19.9 surface marker, distinguished acinar-derived cells (UEA1+CA19.9−) from duct-like cells (UEA1−CA19.9+) and acinar-to-duct-like transdifferentiated cells (UEA1+CA19.9+). mRNA expression analysis of
the acinar-derived (UEA1+CA19.9−) and duct-like (UEA1-CA19.9+) cell fractions with concomitant immunocytochemical analysis of the pancreatospheres revealed acquisition of an embryonic signature in the UEA1+CA19.9− acinar-derived cells characterized by de novo expression of SOX9 and CD142, robust expression of PDX1 and surface expression of GP2. The colocalisation of CD142, a multipotent pancreatic progenitor surface marker, PDX1, SOX9 and GP2 is reminiscent of a cellular state present during human embryonic development. Addition of TGF-beta signalling inhibitor Alk5iII, induced a 28- fold increased KI67-labeling in pancreatospheres, more pronounced in the CD142+GP2+ acinar-derived cells. These findings with human cells underscore the remarkable plasticity of pancreatic exocrine acinar cells, previously described in rodents, and could find applications in the eld of regenerative medicine
Originele taal-2English
Artikelnummer4040
Pagina's (van-tot)1-12
Aantal pagina's12
TijdschriftScientific Reports - Nature
Volume9
Nummer van het tijdschrift1
Vroegere onlinedatum11 mrt 2019
DOI's
StatusPublished - 11 mrt 2019

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