title: Conversion of human pancreatic acinar cells toward a ductal-mesenchymal phenotype and the role of transforming growth factor β and activin signaling.
abstract: OBJECTIVE
  Epithelial-mesenchymal transition may interfere with the differentiation of cultured pancreatic acinar cells toward endocrine cells. Therefore, it will be important to investigate into detail the reprogramming of human pancreatic acinar cells toward a mesenchymal phenotype: the association with acinoductal transdifferentiation, the influence of cell adhesion, and the regulation behind this process.
  
  
  METHODS
  Human exocrine cells, isolated from donor pancreata, were cultured in suspension or as monolayers. Non-genetic lineage tracing, using labeled ulex europaeus agglutinin 1 lectin, was performed, and the role of the transforming growth factor (TGF-β) superfamily was investigated.
  
  
  RESULTS
  After 7 days in monolayer culture, the human acinar cells coexpressed the mesenchymal marker vimentin and the ductal marker Sox9. However, when the human exocrine cells were cultured in suspension, epithelial-mesenchymal transition was not observed. The spontaneous transition of the human acinar cells toward a ductal and mesenchymal phenotype was decreased by inhibition of the TGF-β and activin signaling pathways.
  
  
  CONCLUSIONS
  The human acinar cells spontaneously undergo TGF-β- regulated reprogramming in the monolayer culture. These observations are helpful to develop culture methods for the in vitro reprogramming of pancreatic exocrine to endocrine cells. They are also of potential interest for studies on exocrine acinar cells in the development of pancreatic cancer.
authors.affiliation: From the *Cell Differentiation Laboratory, and †Cell Therapy Laboratory, Diabetes Research Center, Vrije Universiteit Brussel, Brussels, Belgium.
authors.forename: Evelien
authors.initials: E
authors.lastname: De Waele
authors.forename: Elke
authors.initials: E
authors.lastname: Wauters
authors.forename: Zhidong
authors.initials: Z
authors.lastname: Ling
authors.forename: Luc
authors.initials: L
authors.lastname: Bouwens
mesh_terms: D061354:Acinar Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D028341:Activins / Q000037:antagonists & inhibitors / Q000502:physiology*; D001549:Benzamides / Q000494:pharmacology*; D015415:Biomarkers; D055415:Bone Morphogenetic Protein 4 / Q000037:antagonists & inhibitors / Q000494:pharmacology; D018929:Cell Culture Techniques; D019070:Cell Lineage; D002478:Cells, Cultured; D004149:Dioxoles / Q000494:pharmacology*; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects*; D006801:Humans; D046790:Pancreas, Exocrine / Q000166:cytology*; D037121:Plant Lectins; D018125:Receptors, Transforming Growth Factor beta / Q000037:antagonists & inhibitors; D055758:SOX9 Transcription Factor / Q000096:biosynthesis / Q000235:genetics; D015398:Signal Transduction / Q000187:drug effects; D000071250:Snail Family Transcription Factors; D013535:Suspensions; D055411:TGF-beta Superfamily Proteins / Q000037:antagonists & inhibitors / Q000502:physiology*; D014157:Transcription Factors / Q000096:biosynthesis / Q000235:genetics; D014746:Vimentin / Q000096:biosynthesis / Q000235:genetics
chemical_list: C459179:4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide; C525809:BMP4 protein, human; D001549:Benzamides; D015415:Biomarkers; D055415:Bone Morphogenetic Protein 4; D004149:Dioxoles; D037121:Plant Lectins; D018125:Receptors, Transforming Growth Factor beta; D055758:SOX9 Transcription Factor; C527932:SOX9 protein, human; D000071250:Snail Family Transcription Factors; D013535:Suspensions; D055411:TGF-beta Superfamily Proteins; D014157:Transcription Factors; C036850:Ulex europaeus lectins; D014746:Vimentin; D028341:Activins