title: Duct cells contribute to regeneration of endocrine and acinar cells following pancreatic damage in adult mice.
abstract: OBJECTIVE
  There have been conflicting results on a cell of origin in pancreatic regeneration. These discrepancies predominantly stem from lack of specific markers for the pancreatic precursors/stem cells, as well as differences in the targeted cells and severity of tissue injury in the experimental models so far proposed. We attempted to create a model that used diphtheria toxin receptor (DTR) to ablate specific cell populations, control the extent of injury, and avoid induction of the inflammatory response.
  
  
  METHODS
  To target specific types of pancreatic cells, we crossed R26DTR or R26DTR/lacZ mice with transgenic mice that express the Cre recombinase in the pancreas, under control of the Pdx1 (global pancreatic) or elastase (acinar-specific) promoters.
  
  
  RESULTS
  Exposure of PdxCre;R26DTR mice to diphtheria toxin resulted in extensive ablation of acinar and endocrine tissues but not ductal cells. Surviving cells within the ductal compartment contributed to regeneration of endocrine and acinar cells via recapitulation of the embryonic pancreatic developmental program. However, following selective ablation of acinar tissue in ElaCreERT2;R26DTR mice, regeneration likely occurred by reprogramming of ductal cells to acinar lineage.
  
  
  CONCLUSIONS
  In the pancreas of adult mice, epithelial cells within the ductal compartment contribute to regeneration of endocrine and acinar cells. The severity of injury determines the regenerative mechanisms and cell types that contribute to this process.
authors.affiliation: Department of Surgery, Children's Hospital of Pittsburgh, University of Pittsburgh Medical Center, Rangos Research Center, Pittsburgh, Pennsylvania 15224, USA.
authors.forename: Angela
authors.initials: A
authors.lastname: Criscimanna
authors.forename: Julie A
authors.initials: JA
authors.lastname: Speicher
authors.forename: Golbahar
authors.initials: G
authors.lastname: Houshmand
authors.forename: Chiyo
authors.initials: C
authors.lastname: Shiota
authors.forename: Krishna
authors.initials: K
authors.lastname: Prasadan
authors.forename: Baoan
authors.initials: B
authors.lastname: Ji
authors.forename: Craig D
authors.initials: CD
authors.lastname: Logsdon
authors.forename: George K
authors.initials: GK
authors.lastname: Gittes
authors.forename: Farzad
authors.initials: F
authors.lastname: Esni
mesh_terms: D000818:Animals; D019070:Cell Lineage; D049109:Cell Proliferation; D002470:Cell Survival; D004167:Diphtheria Toxin; D004195:Disease Models, Animal; D004847:Epithelial Cells / Q000378:metabolism / Q000473:pathology*; D066257:Heparin-binding EGF-like Growth Factor; D018398:Homeodomain Proteins / Q000235:genetics; D019426:Integrases / Q000235:genetics; D036341:Intercellular Signaling Peptides and Proteins / Q000096:biosynthesis / Q000235:genetics; D007515:Islets of Langerhans / Q000378:metabolism / Q000473:pathology*; D007763:Lac Operon; D051379:Mice; D008822:Mice, Transgenic; D046790:Pancreas, Exocrine / Q000378:metabolism / Q000473:pathology*; D010182:Pancreatic Diseases / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D010183:Pancreatic Ducts / Q000378:metabolism / Q000473:pathology*; D010196:Pancreatic Elastase / Q000235:genetics; D011506:Proteins / Q000235:genetics; D022661:RNA, Untranslated; D012038:Regeneration; D013997:Time Factors; D015534:Trans-Activators / Q000235:genetics
chemical_list: D004167:Diphtheria Toxin; C110853:Gt(ROSA)26Sor non-coding RNA, mouse; C587884:Hbegf protein, mouse; D066257:Heparin-binding EGF-like Growth Factor; D018398:Homeodomain Proteins; D036341:Intercellular Signaling Peptides and Proteins; D011506:Proteins; D022661:RNA, Untranslated; D015534:Trans-Activators; C084010:pancreatic and duodenal homeobox 1 protein; C045073:Cre recombinase; D019426:Integrases; D010196:Pancreatic Elastase