title: Induced Mist1 expression promotes remodeling of mouse pancreatic acinar cells.
abstract: OBJECTIVE
  Early embryogenesis involves cell fate decisions that define the body axes and establish pools of progenitor cells. Development does not stop once lineages are specified; cells continue to undergo specific maturation events, and changes in gene expression patterns lead to their unique physiological functions. Secretory pancreatic acinar cells mature postnatally to synthesize large amounts of protein, polarize, and communicate with other cells. The transcription factor MIST1 is expressed by only secretory cells and regulates maturation events. MIST1-deficient acinar cells in mice do not establish apical-basal polarity, properly position zymogen granules, or communicate with adjacent cells, disrupting pancreatic function. We investigated whether MIST1 directly induces and maintains the mature phenotype of acinar cells.
  
  
  METHODS
  We analyzed the effects of Cre-mediated expression of Mist1 in adult Mist1-deficient (Mist1(KO)) mice. Pancreatic tissues were collected and analyzed by light and electron microscopy, immunohistochemistry, real-time polymerase chain reaction analysis, and chromatin immunoprecipitation. Primary acini were isolated from mice and analyzed in amylase secretion assays.
  
  
  RESULTS
  Induced expression of Mist1 in adult Mist1(KO) mice restored wild-type gene expression patterns in acinar cells. The acinar cells changed phenotypes, establishing apical-basal polarity, increasing the size of zymogen granules, reorganizing the cytoskeletal network, communicating intercellularly (by synthesizing gap junctions), and undergoing exocytosis.
  
  
  CONCLUSIONS
  The exocrine pancreas of adult mice can be remodeled by re-expression of the transcription factor MIST1. MIST1 regulates acinar cell maturation and might be used to repair damaged pancreata in patients with pancreatic disorders.
authors.affiliation: Department of Biological Sciences, Purdue University, West Lafayette, IN, USA.
authors.forename: Daniel
authors.initials: D
authors.lastname: Direnzo
authors.forename: David A
authors.initials: DA
authors.lastname: Hess
authors.forename: Barbara
authors.initials: B
authors.lastname: Damsz
authors.forename: Judy E
authors.initials: JE
authors.lastname: Hallett
authors.forename: Brett
authors.initials: B
authors.lastname: Marshall
authors.forename: Chirayu
authors.initials: C
authors.lastname: Goswami
authors.forename: Yunlong
authors.initials: Y
authors.lastname: Liu
authors.forename: Tye
authors.initials: T
authors.lastname: Deering
authors.forename: Raymond J
authors.initials: RJ
authors.lastname: Macdonald
authors.forename: Stephen F
authors.initials: SF
authors.lastname: Konieczny
mesh_terms: D061354:Acinar Cells / Q000378:metabolism / Q000502:physiology*; D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000172:deficiency / Q000378:metabolism*; D015415:Biomarkers / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008854:Microscopy, Electron; D046790:Pancreas, Exocrine / Q000166:cytology* / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D015398:Signal Transduction
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D015415:Biomarkers; C491312:Bhlha15 protein, mouse