A Nuclear Role for miR-9 and Argonaute Proteins in Balancing Quiescent and Activated Neural Stem Cell States
| Autor: | Laure Bally-Cuif, François Guillemot, Marion Coolen, Delphine Cussigh, Noelia Urbán, Isabelle Maria Blomfield, Shauna Katz |
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| Přispěvatelé: | Institut des Neurosciences Paris-Saclay (NeuroPSI), Université Paris-Sud - Paris 11 (UP11)-Centre National de la Recherche Scientifique (CNRS), Biologie du Développement et Cellules souches (CNRS UMR3738), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), The Francis Crick Institute [London], Work in the L.B.-C. lab was funded by the EU project ZF-Health (FP7/2010-2015 grant agreement 242048), the ANR (grant ANR-2012-BSV4-0004-01), the Ecole des Neurosciences de Paris (ENP), the FRM (FRP 'Equipe' DEQ20120323692), and the European Research Council (AdG 322936). M.C. is supported by INSERM. S.K. was recipient of fellowships from the ENP, the DIM Cerveau et Pensée of Région Ile de France, and The Company of Biologists Limited (Travelling Fellowship DEVTF-140404). N.U. was supported by the BBSRC (BB/K005316/1). Work in F.G.’s lab was supported by The Francis Crick Institute that receives its core funding from Cancer Research UK (FC001089), the UK Medical Research Council (FC001089), and the Wellcome Trust (FC001089)., We thank members of the ZEN lab and Eric Miska for their critical input. We are grateful to J. Ninkovic for the 4C4 antibody., ANR-12-BSV4-0004,HOMEOSTEM,Contrôle moléculaire et cellulaire de l'homéostasie des zones germinatives dans le télencéphale adulte chez le poisson zébré(2012), European Project: 242048,EC:FP7:HEALTH,FP7-HEALTH-2009-two-stage,ZF-HEALTH(2010), European Project: 322936,EC:FP7:ERC,ERC-2012-ADG_20120314,SYSTEMATICS(2013), Département de Biologie du Développement et Cellules souches - Department of Developmental and Stem Cell Biology, Institut Pasteur [Paris] |
| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
MESH: Neural Stem Cells
MESH: Signal Transduction 0301 basic medicine Telencephalon Aging [SDV]Life Sciences [q-bio] radial glia MESH: Cell Cycle neural stem cell Mice MESH: Argonaute Proteins Neural Stem Cells MESH: Aging MESH: Animals lcsh:QH301-705.5 Zebrafish reproductive and urinary physiology Receptors Notch Neurogenesis Cell Cycle Argonaute Cell cycle MESH: Gene Expression Regulation Neural stem cell Cell biology adult neurogenesis medicine.anatomical_structure Argonaute Proteins MESH: Neuroglia Neuroglia Signal Transduction MESH: Cell Nucleus Notch Notch signaling pathway Biology Models Biological General Biochemistry Genetics and Molecular Biology Article 03 medical and health sciences medicine Animals quiescence MESH: Zebrafish MESH: Mice Cell Nucleus miR-9 MESH: Models Biological biology.organism_classification zebrafish Cell nucleus MicroRNAs 030104 developmental biology lcsh:Biology (General) nervous system Gene Expression Regulation MESH: Telencephalon MESH: Receptors Notch MESH: MicroRNAs Nuclear localization sequence |
| Zdroj: | Cell Reports Cell Reports, Vol 17, Iss 5, Pp 1383-1398 (2016) Cell Reports, 2016, 17 (5), pp.1383-1398. ⟨10.1016/j.celrep.2016.09.088⟩ Cell Reports, Elsevier Inc, 2016, 17 (5), pp.1383-1398. ⟨10.1016/j.celrep.2016.09.088⟩ |
| ISSN: | 2211-1247 |
| Popis: | Summary Throughout life, adult neural stem cells (NSCs) produce new neurons and glia that contribute to crucial brain functions. Quiescence is an essential protective feature of adult NSCs; however, the establishment and maintenance of this state remain poorly understood. We demonstrate that in the adult zebrafish pallium, the brain-enriched miR-9 is expressed exclusively in a subset of quiescent NSCs, highlighting a heterogeneity within these cells, and is necessary to maintain NSC quiescence. Strikingly, miR-9, along with Argonaute proteins (Agos), is localized to the nucleus of quiescent NSCs, and manipulating their nuclear/cytoplasmic ratio impacts quiescence. Mechanistically, miR-9 permits efficient Notch signaling to promote quiescence, and we identify the RISC protein TNRC6 as a mediator of miR-9/Agos nuclear localization in vivo. We propose a conserved non-canonical role for nuclear miR-9/Agos in controlling the balance between NSC quiescence and activation, a key step in maintaining adult germinal pools. Graphical Abstract Highlights • miR-9 highlights a state heterogeneity among adult quiescent neural stem cells (NSC) • miR-9 maintains NSC quiescence notably through permitting efficient Notch signaling • miR-9, along with Argonaute proteins, is present in the nucleus of adult quiescent NSCs • Active nucleo-cytoplasmic shuttling of miR-9/Ago impacts NSCs quiescence status An essential protective feature of adult neural stem cells is their relative quiescence. Katz et al. identify microRNA-9 as crucial factor that maintains adult NSCs quiescence and sets a heterogeneity within these cells, through a non-canonical nuclear mode of action. |
| Databáze: | OpenAIRE |
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