Transcriptional Dysregulation in Postnatal Glutamatergic Progenitors Contributes to Closure of the Cortical Neurogenic Period.
Cell Reports. 2018-03-01; 22(10): 2567-2574
DOI: 10.1016/j.celrep.2018.02.030
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1. Cell Rep. 2018 Mar 6;22(10):2567-2574. doi: 10.1016/j.celrep.2018.02.030.
Transcriptional Dysregulation in Postnatal Glutamatergic Progenitors Contributes
to Closure of the Cortical Neurogenic Period.
Donega V(1), Marcy G(2), Lo Giudice Q(3), Zweifel S(3), Angonin D(3), Fiorelli
R(4), Abrous DN(5), Rival-Gervier S(6), Koehl M(5), Jabaudon D(7), Raineteau
O(8).
Author information:
(1)Univ Lyon, Université Claude Bernard Lyon 1, Inserm, Stem Cell and Brain
Research Institute U1208, 69500 Bron, France. Electronic address:
.
(2)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.
(3)Univ Lyon, Université Claude Bernard Lyon 1, Inserm, Stem Cell and Brain
Research Institute U1208, 69500 Bron, France.
(4)Brain Research Institute, University of Zürich/ETHZ, Zürich, Switzerland.
(5)Neurocentre Magendie, Neurogenesis and Physiopathology Group, Inserm, U1215,
33077 Bordeaux, France; Université de Bordeaux, 33077 Bordeaux, France.
(6)Stem Cell and Brain Research Institute U1208, Université Claude Bernard Lyon
1, Inserm, INRA, USC1361, 69500 Bron, France.
(7)Department of Basic Neurosciences, University of Geneva, Geneva, Switzerland.
(8)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:
.
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 m6A 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.
DOI: 10.1016/j.celrep.2018.02.030
PMID: 29514086