title: RE1 silencing transcription factor/neuron-restrictive silencing factor regulates expansion of adult mouse subventricular zone-derived neural stem/progenitor cells in vitro.
abstract: Adult neural stem cell (aNSC) activity is tuned by external stimuli through the recruitment of transcription factors. This study examines the RE1 silencing transcription factor (REST) in neural stem/progenitor cells isolated from the subventricular zone of adult mouse brain and provides the first extensive characterization of REST-mediated control of the cellular and molecular properties. This study shows that REST knockdown affects the capacity of progenitor cells to generate neurospheres, reduces cell proliferation, and triggers cell differentiation despite the presence of growth factors. Genome- and transcriptome-wide analyses show that REST binding sites are significantly enriched in genes associated with synaptic transmission and nervous system development and function. Seeking candidate regulators of aNSC function, this study identifies a member of the bone morphogenetic protein (BMP) family, BMP6, the mRNA and protein of which increased after REST knockdown. The results of this study extend previous findings, demonstrating a reciprocal control of REST expression by BMPs. Administration of exogenous BMP6 inhibits aNSC proliferation and induces the expression of the astrocytic marker glial fibrillary acidic protein, highlighting its antimitogenic and prodifferentiative effects. This study suggests that BMP6 produced in a REST-regulated manner together with other signals can contribute to regulation of NSC maintenance and fate.
authors.affiliation: Department of Biology and Biotechnology "Charles Darwin," Sapienza University of Rome, Rome, Italy.|Istituto Pasteur Fondazione Cenci Bolognetti, Sapienza University of Rome, Rome, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Soldati
authors.affiliation: Department of Biology and Biotechnology "Charles Darwin," Sapienza University of Rome, Rome, Italy.
authors.forename: Pasquale
authors.initials: P
authors.lastname: Caramanica
authors.affiliation: Department of Neuroscience, Centre for the Cellular Basis of Behaviour, Institute of Psychiatry, King's College London, London, United Kingdom.
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Burney
authors.affiliation: Department of Biology and Biotechnology "Charles Darwin," Sapienza University of Rome, Rome, Italy.|Center for Life Nanoscience Sapienza, Istituto Italiano di Tecnologia, Rome, Italy.
authors.forename: Camilla
authors.initials: C
authors.lastname: Toselli
authors.affiliation: Department of Neuroscience, Centre for the Cellular Basis of Behaviour, Institute of Psychiatry, King's College London, London, United Kingdom.
authors.forename: Angela
authors.initials: A
authors.lastname: Bithell
authors.affiliation: Department of Biology and Biotechnology "Charles Darwin," Sapienza University of Rome, Rome, Italy.
authors.forename: Gabriella
authors.initials: G
authors.lastname: Augusti-Tocco
authors.affiliation: Genome Institute of Singapore, Singapore.
authors.forename: Lawrence W
authors.initials: LW
authors.lastname: Stanton
authors.affiliation: Department of Biology and Biotechnology "Charles Darwin," Sapienza University of Rome, Rome, Italy.|Center for Life Nanoscience Sapienza, Istituto Italiano di Tecnologia, Rome, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Biagioni
authors.affiliation: Department of Psychiatry, University of Oxford, Warneford Hospital, Oxford, United Kingdom.
authors.forename: Noel J
authors.initials: NJ
authors.lastname: Buckley
authors.affiliation: Department of Biology and Biotechnology "Charles Darwin," Sapienza University of Rome, Rome, Italy.|Istituto Pasteur Fondazione Cenci Bolognetti, Sapienza University of Rome, Rome, Italy.
authors.forename: Emanuele
authors.initials: E
authors.lastname: Cacci
mesh_terms: D053687:Adult Stem Cells / Q000502:physiology*; D000818:Animals; D055418:Bone Morphogenetic Protein 6 / Q000502:physiology; D002454:Cell Differentiation / Q000502:physiology; D049109:Cell Proliferation / Q000502:physiology; D002478:Cells, Cultured; D020868:Gene Silencing / Q000502:physiology*; D006801:Humans; D020547:Lateral Ventricles / Q000166:cytology* / Q000502:physiology*; D008297:Male; D051379:Mice; D058953:Neural Stem Cells / Q000502:physiology*; D012097:Repressor Proteins / Q000502:physiology*; D014157:Transcription Factors / Q000502:physiology; D000099229:RE1-Silencing Transcription Factor
chemical_list: D055418:Bone Morphogenetic Protein 6; D012097:Repressor Proteins; D014157:Transcription Factors; D000099229:RE1-Silencing Transcription Factor; C525817:Bmp6 protein, mouse
keywords: REST; bone morphogenetic proteins; cell differentiation; gene expression; neural stem cells; repressor element 1 (RE1)-silencing transcription factor