title: Embryonic ductal plate cells give rise to cholangiocytes, periportal hepatocytes, and adult liver progenitor cells.
abstract: BACKGROUND& AIMS: Embryonic biliary precursor cells form a periportal sheet called the ductal plate, which is progressively remodeled to generate intrahepatic bile ducts. A limited number of ductal plate cells participate in duct formation; those not involved in duct development are believed to involute by apoptosis. Moreover, cells that express the SRY-related HMG box transcription factor 9 (SOX9), which include the embryonic ductal plate cells, were proposed to continuously supply the liver with hepatic cells. We investigated the role of the ductal plate in hepatic morphogenesis.
  
  
  METHODS
  Apoptosis and proliferation were investigated by immunostaining of mouse and human fetal liver tissue. The postnatal progeny of SOX9-expressing ductal plate cells was analyzed after genetic labeling, at the ductal plate stage, by Cre-mediated recombination of a ROSA26RYFP reporter allele. Inducible Cre expression was induced by SOX9 regulatory regions, inserted in a bacterial artificial chromosome. Livers were studied from mice under normal conditions and during diet-induced regeneration.
  
  
  RESULTS
  Ductal plate cells did not undergo apoptosis and showed limited proliferation. They generated cholangiocytes lining interlobular bile ducts, bile ductules, and canals of Hering, as well as periportal hepatocytes. Oval cells that appeared during regeneration also derived from the ductal plate. We did not find that liver homeostasis required a continuous supply of cells from SOX9-expressing progenitors.
  
  
  CONCLUSIONS
  The ductal plate gives rise to cholangiocytes lining the intrahepatic bile ducts, including its most proximal segments. It also generates periportal hepatocytes and adult hepatic progenitor cells.
authors.affiliation: de Duve Institute, Université Catholique de Louvain, Brussels, Belgium.
authors.forename: Rodolphe
authors.initials: R
authors.lastname: Carpentier
authors.forename: Regina Español
authors.initials: RE
authors.lastname: Suñer
authors.forename: Noémi
authors.initials: N
authors.lastname: van Hul
authors.forename: Janel L
authors.initials: JL
authors.lastname: Kopp
authors.forename: Jean-Bernard
authors.initials: JB
authors.lastname: Beaudry
authors.forename: Sabine
authors.initials: S
authors.lastname: Cordi
authors.forename: Aline
authors.initials: A
authors.lastname: Antoniou
authors.forename: Peggy
authors.initials: P
authors.lastname: Raynaud
authors.forename: Sébastien
authors.initials: S
authors.lastname: Lepreux
authors.forename: Patrick
authors.initials: P
authors.lastname: Jacquemin
authors.forename: Isabelle A
authors.initials: IA
authors.lastname: Leclercq
authors.forename: Maike
authors.initials: M
authors.lastname: Sander
authors.forename: Frédéric P
authors.initials: FP
authors.lastname: Lemaigre
mesh_terms: D053687:Adult Stem Cells / Q000378:metabolism / Q000502:physiology*; D000818:Animals; D017209:Apoptosis; D001653:Bile Ducts, Intrahepatic / Q000196:embryology* / Q000378:metabolism; D002454:Cell Differentiation; D019070:Cell Lineage; D049109:Cell Proliferation; D022202:Chromosomes, Artificial, Bacterial; D053595:Embryonic Stem Cells / Q000378:metabolism / Q000502:physiology*; D005455:Fluorescent Antibody Technique; D005865:Gestational Age; D022781:Hepatocytes / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D019426:Integrases / Q000235:genetics; D008099:Liver / Q000196:embryology* / Q000378:metabolism; D008115:Liver Regeneration; D008164:Luminescent Proteins / Q000096:biosynthesis / Q000235:genetics; D051379:Mice; D008822:Mice, Transgenic; D018613:Microscopy, Confocal; D008856:Microscopy, Fluorescence; D011506:Proteins / Q000235:genetics; D022661:RNA, Untranslated; D055758:SOX9 Transcription Factor / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism
chemical_list: C110853:Gt(ROSA)26Sor non-coding RNA, mouse; D008164:Luminescent Proteins; D011506:Proteins; D022661:RNA, Untranslated; D055758:SOX9 Transcription Factor; C527932:SOX9 protein, human; C527933:Sox9 protein, mouse; C045073:Cre recombinase; D019426:Integrases