title: Genes inducing iPS phenotype play a role in hepatocyte survival and proliferation in vitro and liver regeneration in vivo.
abstract: Reprogramming factors have been used to induce pluripotent stem cells as an alternative to somatic cell nuclear transfer technology in studies targeting disease models and regenerative medicine. The neuronal repressor RE-1 silencing transcription factor (REST) maintains self-renewal and pluripotency in mouse embryonic stem cells by maintaining the expression of Oct3/4, Nanog, and cMyc. We report that primary hepatocytes express REST and most of the reprogramming factors in culture. Their expression is up-regulated by hepatocyte growth factor (HGF) and epidermal growth factor (EGF). REST inhibition results in down-regulation of reprogramming factor expression, increased apoptosis, decreased proliferation, and cell death. The reprogramming factors are also up-regulated after 70% partial hepatectomy in vivo.
  
  
  CONCLUSIONS
  These findings show that genes inducing the iPS phenotype, even though expressed at lower levels than embryonic stem cells, nonetheless are associated with control of apoptosis and cell proliferation in hepatocytes in culture and may play a role in such processes during liver regeneration.
authors: Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA.
authors: Vishakha S
authors: VS
authors: Bhave
authors: Shirish
authors: S
authors: Paranjpe
authors: William C
authors: WC
authors: Bowen
authors: Shashikiran
authors: S
authors: Donthamsetty
authors: Aaron W
authors: AW
authors: Bell
authors: Jaspal S
authors: JS
authors: Khillan
authors: George K
authors: GK
authors: Michalopoulos
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D017209:Apoptosis / Q000235:genetics*; D015153:Blotting, Western; D049109:Cell Proliferation; D002470:Cell Survival / Q000235:genetics; D002478:Cells, Cultured; D056970:Co-Repressor Proteins; D018076:DNA, Complementary / Q000096:biosynthesis; D004195:Disease Models, Animal; D022781:Hepatocytes / Q000166:cytology* / Q000378:metabolism; D066298:In Vitro Techniques; D057026:Induced Pluripotent Stem Cells / Q000378:metabolism; D008115:Liver Regeneration / Q000235:genetics*; D008297:Male; D051379:Mice; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000378:metabolism; D010641:Phenotype; D012313:RNA / Q000032:analysis; D011916:Rats, Inbred F344; D060888:Real-Time Polymerase Chain Reaction / Q000379:methods; D012016:Reference Values; D012097:Repressor Proteins / Q000235:genetics* / Q000378:metabolism
chemical_list: D056970:Co-Repressor Proteins; D018076:DNA, Complementary; D009419:Nerve Tissue Proteins; C485650:Rcor2 protein, mouse; D012097:Repressor Proteins; D012313:RNA