title: Liver progenitor cells yield functional hepatocytes in response to chronic liver injury in mice.
abstract: OBJECTIVE
  Self-renewal of mature hepatocytes promotes homeostasis and regeneration of adult liver. However, recent studies have indicated that liver progenitor cells (LPC) could give rise to hepatic epithelial cells during normal turnover of the liver and after acute injury. We investigated the capacity of LPC to differentiate into hepatocytes in vivo and contribute to liver regeneration.
  
  
  METHODS
  We performed lineage tracing experiments, using mice that express tamoxifen-inducible Cre recombinase under control of osteopontin regulatory region crossed with yelow fluorescent protein reporter mice, to follow the fate of LPC and biliary cells. Adult mice received partial (two-thirds) hepatectomy, acute or chronic administration of carbon tetrachloride (CCl(4)), choline-deficient diet supplemented with ethionine, or 3,5-diethoxycarbonyl-1,4-dihydrocollidine diet.
  
  
  RESULTS
  LPC and/or biliary cells generated 0.78% and 2.45% of hepatocytes during and upon recovery of mice from liver injury, respectively. Repopulation efficiency by LPC and/or biliary cells increased when extracellular matrix and laminin deposition were reduced. The newly formed hepatocytes integrated into hepatic cords, formed biliary canaliculi, expressed hepato-specific enzymes, accumulated glycogen, and proliferated in response to partial hepatectomy, as neighboring native hepatocytes. By contrast, LPC did not contribute to hepatocyte regeneration during normal liver homeostasis, in response to surgical or toxic loss of liver mass, during chronic liver injury (CCl(4)-induced), or during ductular reactions.
  
  
  CONCLUSIONS
  LPC or biliary cells terminally differentiate into functional hepatocytes in mice with liver injury.
authors.affiliation: Laboratory of Hepato-Gastroenterology, Institut de Recherche Expérimentale et Clinique, Université catholique de Louvain, Brussels, Belgium.
authors.forename: Regina
authors.initials: R
authors.lastname: Español-Suñer
authors.forename: Rodolphe
authors.initials: R
authors.lastname: Carpentier
authors.forename: Noémi
authors.initials: N
authors.lastname: Van Hul
authors.forename: Vanessa
authors.initials: V
authors.lastname: Legry
authors.forename: Younes
authors.initials: Y
authors.lastname: Achouri
authors.forename: Sabine
authors.initials: S
authors.lastname: Cordi
authors.forename: Patrick
authors.initials: P
authors.lastname: Jacquemin
authors.forename: Frédéric
authors.initials: F
authors.lastname: Lemaigre
authors.forename: Isabelle A
authors.initials: IA
authors.lastname: Leclercq
mesh_terms: D000818:Animals; D002251:Carbon Tetrachloride / Q000009:adverse effects; D002454:Cell Differentiation / Q000502:physiology*; D056486:Chemical and Drug Induced Liver Injury / Q000209:etiology / Q000473:pathology*; D002796:Choline Deficiency / Q000150:complications; D058750:Epithelial-Mesenchymal Transition / Q000502:physiology; D005260:Female; D006498:Hepatectomy / Q000009:adverse effects; D022781:Hepatocytes / Q000166:cytology*; D006706:Homeostasis / Q000502:physiology; D008099:Liver / Q000166:cytology* / Q000502:physiology; D008115:Liver Regeneration / Q000502:physiology*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D023421:Models, Animal; D013234:Stem Cells / Q000166:cytology*
chemical_list: D002251:Carbon Tetrachloride