Transcriptional Dysregulation in Postnatal Glutamatergic Progenitors Contributes to Closure of the Cortical Neurogenic Period.
Autor: | Donega V; Univ Lyon, Université Claude Bernard Lyon 1, Inserm, Stem Cell and Brain Research Institute U1208, 69500 Bron, France. Electronic address: v.donega@umcutrecht.nl., Marcy G; Univ Lyon, Université Claude Bernard Lyon 1, Inserm, Stem Cell and Brain Research Institute U1208, 69500 Bron, France; Neurogenetics Department, Ecole Pratique des Hautes Etudes, PSL Research University, 75014 Paris, France., Lo Giudice Q; Univ Lyon, Université Claude Bernard Lyon 1, Inserm, Stem Cell and Brain Research Institute U1208, 69500 Bron, France., Zweifel S; Univ Lyon, Université Claude Bernard Lyon 1, Inserm, Stem Cell and Brain Research Institute U1208, 69500 Bron, France., Angonin D; Univ Lyon, Université Claude Bernard Lyon 1, Inserm, Stem Cell and Brain Research Institute U1208, 69500 Bron, France., Fiorelli R; Brain Research Institute, University of Zürich/ETHZ, Zürich, Switzerland., Abrous DN; Neurocentre Magendie, Neurogenesis and Physiopathology Group, Inserm, U1215, 33077 Bordeaux, France; Université de Bordeaux, 33077 Bordeaux, France., Rival-Gervier S; Stem Cell and Brain Research Institute U1208, Université Claude Bernard Lyon 1, Inserm, INRA, USC1361, 69500 Bron, France., Koehl M; Neurocentre Magendie, Neurogenesis and Physiopathology Group, Inserm, U1215, 33077 Bordeaux, France; Université de Bordeaux, 33077 Bordeaux, France., Jabaudon D; Department of Basic Neurosciences, University of Geneva, Geneva, Switzerland., Raineteau O; Univ Lyon, Université Claude Bernard Lyon 1, Inserm, Stem Cell and Brain Research Institute U1208, 69500 Bron, France; Brain Research Institute, University of Zürich/ETHZ, Zürich, Switzerland. Electronic address: olivier.raineteau@inserm.fr. |
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Jazyk: | angličtina |
Zdroj: | Cell reports [Cell Rep] 2018 Mar 06; Vol. 22 (10), pp. 2567-2574. |
DOI: | 10.1016/j.celrep.2018.02.030 |
Abstrakt: | Progenitors of cortical glutamatergic neurons (Glu progenitors) are usually thought to switch fate before birth to produce astrocytes. We used fate-mapping approaches to show that a large fraction of Glu progenitors persist in the postnatal forebrain after closure of the cortical neurogenesis period. Postnatal Glu progenitors do not accumulate during embryonal development but are produced by embryonal radial glial cells that persist after birth in the dorsal subventricular zone and continue to give rise to cortical neurons, although with low efficiency. Single-cell RNA sequencing reveals a dysregulation of transcriptional programs, which parallels changes in m 6 A methylation and correlates with the gradual decline in cortical neurogenesis observed in vivo. Rescuing experiments show that postnatal progenitors are partially permissive to genetic and pharmacological manipulations. Our study provides an in-depth characterization of postnatal Glu progenitors and identifies potential therapeutic targets for promoting brain repair. (Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.) |
Databáze: | MEDLINE |
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