title: Hepatoblast-like progenitor cells derived from embryonic stem cells can repopulate livers of mice.
abstract: OBJECTIVE
  Hepatocyte-like cells can be derived from pluripotent stem cells such as embryonic stem (ES) cells, but ES cell-derived hepatic cells with extensive capacity to repopulate liver have not been identified. We aimed to identify and purify ES cell-derived hepatoblast-like progenitor cells and to explore their capacity for liver repopulation in mice after in vitro expansion.
  
  
  METHODS
  Unmanipulated mouse ES cells were cultured under defined conditions and allowed to undergo stepwise hepatic differentiation. The derived hepatic cells were examined by morphologic, fluorescence-activated cell sorting, gene expression, and clonal expansion analyses. The capacities of ES cell-derived hepatic progenitor cells to repopulate liver were investigated in mice that were deficient in fumarylacetoacetate hydrolase (Fah) (a model of liver injury).
  
  
  RESULTS
  Mouse ES cells were induced to differentiate into a population that contained hepatic progenitor cells; this population included cells that expressed epithelial cell adhesion molecule (EpCAM) but did not express c-Kit. Clonal hepatic progenitors that arose from single c-Kit(-)EpCAM(+) cells could undergo long-term expansion and maintain hepatoblast-like characteristics. Enriched c-Kit(-)EpCAM(+) cells and clonally expanded hepatic progenitor cells repopulated the livers of Fah-deficient mice without inducing tumorigenesis.
  
  
  CONCLUSIONS
  ES cell-derived c-Kit(-)EpCAM(+) cells contain a population of hepatoblast-like progenitor cells that can repopulate livers of mice.
authors.affiliation: Laboratory of Molecular Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Shanghai, China.
authors.forename: Fuming
authors.initials: F
authors.lastname: Li
authors.forename: Pingyu
authors.initials: P
authors.lastname: Liu
authors.forename: Changcheng
authors.initials: C
authors.lastname: Liu
authors.forename: Dao
authors.initials: D
authors.lastname: Xiang
authors.forename: Li
authors.initials: L
authors.lastname: Deng
authors.forename: Wenlin
authors.initials: W
authors.lastname: Li
authors.forename: Kirk
authors.initials: K
authors.lastname: Wangensteen
authors.forename: Jianguo
authors.initials: J
authors.lastname: Song
authors.forename: Yue
authors.initials: Y
authors.lastname: Ma
authors.forename: Lijian
authors.initials: L
authors.lastname: Hui
authors.forename: Lixin
authors.initials: L
authors.lastname: Wei
authors.forename: Lingsong
authors.initials: L
authors.lastname: Li
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Ding
authors.forename: Yiping
authors.initials: Y
authors.lastname: Hu
authors.forename: Zhiying
authors.initials: Z
authors.lastname: He
authors.forename: Xin
authors.initials: X
authors.lastname: Wang
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000502:physiology; D002455:Cell Division / Q000502:physiology; D002469:Cell Separation / Q000379:methods; D002478:Cells, Cultured; D004195:Disease Models, Animal; D053595:Embryonic Stem Cells / Q000166:cytology* / Q000378:metabolism; D006085:Graft Survival / Q000502:physiology; D022781:Hepatocytes / Q000166:cytology*; D006867:Hydrolases / Q000235:genetics; D008107:Liver Diseases / Q000473:pathology* / Q000628:therapy*; D008115:Liver Regeneration; D051379:Mice; D008817:Mice, Mutant Strains; D019009:Proto-Oncogene Proteins c-kit / Q000378:metabolism; D033581:Stem Cell Transplantation
chemical_list: D019009:Proto-Oncogene Proteins c-kit; D006867:Hydrolases; C020156:fumarylacetoacetase