title: A Role for RE-1-Silencing Transcription Factor in Embryonic Stem Cells Cardiac Lineage Specification.
abstract: During development, lineage specification is controlled by several signaling pathways involving various transcription factors (TFs). Here, we studied the RE-1-silencing transcription factor (REST) and identified an important role of this TF in cardiac differentiation. Using mouse embryonic stem cells (ESC) to model development, we found that REST knockout cells lost the ability to differentiate into the cardiac lineage. Detailed analysis of specific lineage markers expression showed selective downregulation of endoderm markers in REST-null cells, thus contributing to a loss of cardiogenic signals. REST regulates cardiac differentiation of ESCs by negatively regulating the Wnt/β-catenin signaling pathway and positively regulating the cardiogenic TF Gata4. We propose here a new role for REST in cell fate specification besides its well-known repressive role of neuronal differentiation.
authors: Stem Cell and Regenerative Biology, Genome Institute of Singapore, Singapore.|Stem Cell and Brain Research Institute, INSERM U1208, 69500 Bron, France.|University of Lyon, University of Lyon I, 69003 Lyon, France.
authors: Irene
authors: I
authors: Aksoy
authors: Stem Cell and Brain Research Institute, INSERM U1208, 69500 Bron, France.|University of Lyon, University of Lyon I, 69003 Lyon, France.
authors: Guillaume
authors: G
authors: Marcy
authors: Stem Cell and Regenerative Biology, Genome Institute of Singapore, Singapore.
authors: Jiaxuan
authors: J
authors: Chen
authors: Stem Cell and Regenerative Biology, Genome Institute of Singapore, Singapore.
authors: Ushashree
authors: U
authors: Divakar
authors: Stem Cell and Regenerative Biology, Genome Institute of Singapore, Singapore.
authors: Vibhor
authors: V
authors: Kumar
authors: Stem Cell and Regenerative Biology, Genome Institute of Singapore, Singapore.
authors: Daniel
authors: D
authors: John-Sanchez
authors: Stem Cell and Regenerative Biology, Genome Institute of Singapore, Singapore.
authors: Mehran
authors: M
authors: Rahmani
authors: Department of Psychiatry, University of Oxford, Warneford Hospital, Headington, Oxford, UK.
authors: Noel J
authors: NJ
authors: Buckley
authors: Stem Cell and Regenerative Biology, Genome Institute of Singapore, Singapore.|School of Biological Sciences, Nanyang Technological University, Singapore.|Department of Biological Sciences, National University of Singapore, Singapore.
authors: Lawrence W
authors: LW
authors: Stanton
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000235:genetics*; D019070:Cell Lineage / Q000235:genetics; D050991:GATA4 Transcription Factor / Q000096:biosynthesis* / Q000235:genetics; D018507:Gene Expression Regulation, Developmental; D051379:Mice; D018345:Mice, Knockout; D000066450:Mouse Embryonic Stem Cells / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics*; D060449:Wnt Signaling Pathway; D000099229:RE1-Silencing Transcription Factor
chemical_list: D050991:GATA4 Transcription Factor; D012097:Repressor Proteins; D000099229:RE1-Silencing Transcription Factor; C484171:Gata4 protein, mouse
keywords: Cardiac lineage; Embryonic stem cells; Endoderm; GATA4; REST; Wnt signaling