title: Epigenetic Modulators Enhance Constitutive and Liver-Specific Reporter Expression in Murine Liver Progenitor Cell Lines.
abstract: Stem cells expressing reporter constructs are extremely useful for their tracking in vivo or for determining cell lineage fate in vivo and in vitro. We generated liver progenitor cell (LPC) lines from actin-EGFP and TAT-GRE-lacZ mice. LPCs from the actin-EGFP mouse facilitate cell tracing following transplant as the reporter is constitutively expressed. LPCs from the TAT-GRE-lacZ mouse express β-galactosidase under the control of the tyrosine aminotransferase (TAT) promoter and are only active in mature hepatocytes. We found that the utility of such LPC lines becomes severely limited by downregulation of transgene expression following extended culture. We show that epigenetic mechanisms are responsible for suppressing expression of both transgenes. Enhancement of transgene expression in both LPC lines was achieved by treating the cell lines with either the histone acetylating agent sodium butyrate or the DNA demethylating agent 5-azacytidine.
authors.affiliation: 1 The Centre for Medical Research, Harry Perkins Institute of Medical Research , Nedlands, WA, Australia .
authors.forename: Luke Aris
authors.initials: LA
authors.lastname: Diepeveen
authors.affiliation: 1 The Centre for Medical Research, Harry Perkins Institute of Medical Research , Nedlands, WA, Australia .|2 Center for Cell Therapy and Regenerative Medicine, School of Medicine and Pharmacology, Crawley, WA, Australia .
authors.forename: Michel Elyse
authors.initials: ME
authors.lastname: Watson
authors.affiliation: 3 School of Chemistry and Biochemistry, University of Western Australia , Crawley, WA, Australia .
authors.forename: Sarah Beth
authors.initials: SB
authors.lastname: McSpadden
authors.affiliation: 3 School of Chemistry and Biochemistry, University of Western Australia , Crawley, WA, Australia .
authors.forename: Robyn Patricia
authors.initials: RP
authors.lastname: Strauss
authors.affiliation: 3 School of Chemistry and Biochemistry, University of Western Australia , Crawley, WA, Australia .
authors.forename: Bernard Andrew
authors.initials: BA
authors.lastname: Callus
authors.affiliation: 1 The Centre for Medical Research, Harry Perkins Institute of Medical Research , Nedlands, WA, Australia .|2 Center for Cell Therapy and Regenerative Medicine, School of Medicine and Pharmacology, Crawley, WA, Australia .|3 School of Chemistry and Biochemistry, University of Western Australia , Crawley, WA, Australia .
authors.forename: George Cheng
authors.initials: GC
authors.lastname: Yeoh
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D002460:Cell Line; D044127:Epigenesis, Genetic; D017930:Genes, Reporter; D022781:Hepatocytes / Q000378:metabolism*; D008099:Liver / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D009928:Organ Specificity; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism*; D014444:Tyrosine Transaminase
chemical_list: D014444:Tyrosine Transaminase