title: Functional characteristics of reversibly immortalized hepatic progenitor cells derived from mouse embryonic liver.
abstract: OBJECTIVE
  Liver is a vital organ and retains its regeneration capability throughout adulthood, which requires contributions from different cell populations, including liver precursors and intrahepatic stem cells. To overcome the mortality of hepatic progenitors (iHPs) in vitro, we aim to establish reversibly immortalized hepatic progenitor cells from mouse embryonic liver.
  
  
  RESULTS
  Using retroviral system to stably express SV40 T antigen flanked with Cre/LoxP sites, we establish a repertoire of iHP clones with varied differentiation potential. The iHP cells maintain long-term proliferative activity and express varied levels of progenitor markers (Pou5f1/Oct4 and Dlk) and hepatocyte markers (AFP, Alb and ApoB). Five representative iHP clones express hepatic/pancreatic transcription factors HNF3α/Foxa1, HNF3β/Foxa2, and HNF4α/MODY1. Dexamethasone is shown to promote the expression of hepatocyte markers AFP and TAT, along with ICG-uptake and glycogen storage functions in the iHP clones. Cre-mediated removal of SV40 T antigen reverses the proliferative activity of iHP cells. When iHP cells are subcutaneously implanted in athymic nude mice, no tumor formation is observed for up to 8 weeks.
  
  
  CONCLUSIONS
  We demonstrate that the established iHP cells are stable, reversible, and non-tumorigenic hepatic progenitor-like cells, which should be valuable for studying liver organogenesis, metabolic regulations, and hepatic lineage-specific differentiation.
authors.affiliation: Stem Cell Biology and Therapy Laboratory, Ministry of Education Key Laboratory of Child Development and Disorders, the Children's Hospital of Chongqing Medical University, Chongqing, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Bi
authors.forename: Yun
authors.initials: Y
authors.lastname: He
authors.forename: Jiayi
authors.initials: J
authors.lastname: Huang
authors.forename: Yuxi
authors.initials: Y
authors.lastname: Su
authors.forename: Gao-Hui
authors.initials: GH
authors.lastname: Zhu
authors.forename: Yi
authors.initials: Y
authors.lastname: Wang
authors.forename: Min
authors.initials: M
authors.lastname: Qiao
authors.forename: Bing-Qiang
authors.initials: BQ
authors.lastname: Zhang
authors.forename: Hongyu
authors.initials: H
authors.lastname: Zhang
authors.forename: Zhongliang
authors.initials: Z
authors.lastname: Wang
authors.forename: Wei
authors.initials: W
authors.lastname: Liu
authors.forename: Jing
authors.initials: J
authors.lastname: Cui
authors.forename: Quan
authors.initials: Q
authors.lastname: Kang
authors.forename: Zhonglin
authors.initials: Z
authors.lastname: Zhang
authors.forename: Youlin
authors.initials: Y
authors.lastname: Deng
authors.forename: Ruifang
authors.initials: R
authors.lastname: Li
authors.forename: Qian
authors.initials: Q
authors.lastname: Zhang
authors.forename: Ke
authors.initials: K
authors.lastname: Yang
authors.forename: Hue H
authors.initials: HH
authors.lastname: Luu
authors.forename: Rex C
authors.initials: RC
authors.lastname: Haydon
authors.forename: Tong-Chuan
authors.initials: TC
authors.lastname: He
authors.forename: Ni
authors.initials: N
authors.lastname: Tang
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002454:Cell Differentiation / Q000502:physiology; D002460:Cell Line; D049109:Cell Proliferation / Q000502:physiology; D053595:Embryonic Stem Cells / Q000378:metabolism / Q000502:physiology*; D005260:Female; D006003:Glycogen / Q000378:metabolism; D057809:HEK293 Cells; D022781:Hepatocytes / Q000502:physiology*; D006801:Humans; D008099:Liver / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D008819:Mice, Nude; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism
chemical_list: D015415:Biomarkers; D006003:Glycogen