title: Murine embryonic stem cell-derived pancreatic acinar cells recapitulate features of early pancreatic differentiation.
abstract: OBJECTIVE
  Acinar cells constitute 90% of the pancreas epithelium, are polarized, and secrete digestive enzymes. These cells play a crucial role in pancreatitis and pancreatic cancer. However, there are limited models to study normal acinar cell differentiation in vitro. The aim of this work was to generate and characterize purified populations of pancreatic acinar cells from embryonic stem (ES) cells.
  
  
  METHODS
  Reporter ES cells (Ela-pur) were generated that stably expressed both beta-galactosidase and puromycin resistance genes under the control of the elastase I promoter. Directed differentiation was achieved by incubation with conditioned media of cultured fetal pancreatic rudiments and adenoviral-mediated co-expression of p48/Ptf1a and Mist1, 2 basic helix-loop-helix transcription factors crucial for normal pancreatic acinar development and differentiation.
  
  
  RESULTS
  Selected cells expressed multiple markers of acinar cells, including digestive enzymes and proteins of the secretory pathway, indicating activation of a coordinated differentiation program. The genes coding for digestive enzymes were not regulated as a single module, thus recapitulating what occurs during in vivo pancreatic development. The generated cells displayed transient agonist-induced Ca(2+) mobilization and showed a typical response to physiologic concentrations of secretagogues, including enzyme synthesis and secretion. Importantly, these effects did not imply the acquisition of a mixed acinar-ductal phenotype.
  
  
  CONCLUSIONS
  These studies allow the generation of almost pure acinar-like cells from ES cells, providing a normal cell-based model for the study of the acinar differentiation program in vitro.
authors: Cancer Research Program, Institut Municipal d'Investigació Mèdica, Barcelona, Spain.
authors: Meritxell
authors: M
authors: Rovira
authors: Fabien
authors: F
authors: Delaspre
authors: Mohammad
authors: M
authors: Massumi
authors: Selma A
authors: SA
authors: Serra
authors: Miguel Angel
authors: MA
authors: Valverde
authors: Josep
authors: J
authors: Lloreta
authors: Marlène
authors: M
authors: Dufresne
authors: Bruno
authors: B
authors: Payré
authors: Stephen F
authors: SF
authors: Konieczny
authors: Pierre
authors: P
authors: Savatier
authors: Francisco X
authors: FX
authors: Real
authors: Anouchka
authors: A
authors: Skoudy
mesh_terms: D000681:Amylases / Q000235:genetics; D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology; D002217:Carbachol / Q000494:pharmacology; D043422:Carboxypeptidases A / Q000235:genetics; D018929:Cell Culture Techniques / Q000379:methods; D002454:Cell Differentiation / Q000502:physiology; D002455:Cell Division / Q000502:physiology; D002478:Cells, Cultured; D018679:Cholinergic Agonists / Q000494:pharmacology; D002919:Chymotrypsinogen / Q000235:genetics; D053595:Embryonic Stem Cells / Q000166:cytology* / Q000502:physiology* / Q000648:ultrastructure; D005089:Exocytosis / Q000187:drug effects / Q000502:physiology; D018507:Gene Expression Regulation, Developmental; D015971:Gene Expression Regulation, Enzymologic; D017930:Genes, Reporter; D051379:Mice; D016253:Microscopy, Immunoelectron; D046790:Pancreas, Exocrine / Q000166:cytology* / Q000196:embryology*; D010196:Pancreatic Elastase / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics; D014162:Transfection
chemical_list: D000681:Amylases; D051792:Basic Helix-Loop-Helix Proteins; D002217:Carbachol; D043422:Carboxypeptidases A; D018679:Cholinergic Agonists; D002919:Chymotrypsinogen; D010196:Pancreatic Elastase; D014157:Transcription Factors; C491312:Bhlha15 protein, mouse; C062602:transcription factor PTF1