Neonatal brain injury unravels transcriptional and signaling changes underlying the reactivation of cortical progenitors

Summary: Germinal activity persists throughout life within the ventricular-subventricular zone (V-SVZ) of the postnatal forebrain due to the presence of neural stem cells (NSCs). Accumulating evidence points to a recruitment for these cells following early brain injuries and suggests their amenabili...

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Main Authors: Louis Foucault, Timothy Capeliez, Diane Angonin, Celia Lentini, Laurent Bezin, Christophe Heinrich, Carlos Parras, Vanessa Donega, Guillaume Marcy, Olivier Raineteau
Format: Article
Language:English
Published: Elsevier 2024-02-01
Series:Cell Reports
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S2211124724000627
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author Louis Foucault
Timothy Capeliez
Diane Angonin
Celia Lentini
Laurent Bezin
Christophe Heinrich
Carlos Parras
Vanessa Donega
Guillaume Marcy
Olivier Raineteau
author_facet Louis Foucault
Timothy Capeliez
Diane Angonin
Celia Lentini
Laurent Bezin
Christophe Heinrich
Carlos Parras
Vanessa Donega
Guillaume Marcy
Olivier Raineteau
author_sort Louis Foucault
collection DOAJ
description Summary: Germinal activity persists throughout life within the ventricular-subventricular zone (V-SVZ) of the postnatal forebrain due to the presence of neural stem cells (NSCs). Accumulating evidence points to a recruitment for these cells following early brain injuries and suggests their amenability to manipulations. We used chronic hypoxia as a rodent model of early brain injury to investigate the reactivation of cortical progenitors at postnatal times. Our results reveal an increased proliferation and production of glutamatergic progenitors within the dorsal V-SVZ. Fate mapping of V-SVZ NSCs demonstrates their contribution to de novo cortical neurogenesis. Transcriptional analysis of glutamatergic progenitors shows parallel changes in methyltransferase 14 (Mettl14) and Wnt/β-catenin signaling. In agreement, manipulations through genetic and pharmacological activation of Mettl14 and the Wnt/β-catenin pathway, respectively, induce neurogenesis and promote newly-formed cell maturation. Finally, labeling of young adult NSCs demonstrates that pharmacological NSC activation has no adverse effects on the reservoir of V-SVZ NSCs and on their germinal activity.
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spelling doaj.art-94e2692e92984ecd8480dd4def4a48f92024-02-29T05:18:47ZengElsevierCell Reports2211-12472024-02-01432113734Neonatal brain injury unravels transcriptional and signaling changes underlying the reactivation of cortical progenitorsLouis Foucault0Timothy Capeliez1Diane Angonin2Celia Lentini3Laurent Bezin4Christophe Heinrich5Carlos Parras6Vanessa Donega7Guillaume Marcy8Olivier Raineteau9University Lyon, Université Claude Bernard Lyon1, INSERM, Stem Cell and Brain Research Institute U1208, 69500 Bron, France; Corresponding authorUniversity Lyon, Université Claude Bernard Lyon1, INSERM, Stem Cell and Brain Research Institute U1208, 69500 Bron, FranceUniversity Lyon, Université Claude Bernard Lyon1, INSERM, Stem Cell and Brain Research Institute U1208, 69500 Bron, FranceUniversity Lyon, Université Claude Bernard Lyon1, INSERM, Stem Cell and Brain Research Institute U1208, 69500 Bron, FranceUniversity Lyon, Université Claude Bernard Lyon 1, INSERM, Centre de Recherche en Neuroscience de Lyon U1028 - CNRS UMR5292, 69500 Bron, FranceUniversity Lyon, Université Claude Bernard Lyon1, INSERM, Stem Cell and Brain Research Institute U1208, 69500 Bron, FranceParis Brain Institute, Sorbonne Université, INSERM U1127, CNRS UMR 7225, Hôpital Pitié-Salpêtrière, 75013 Paris, FranceUniversity Lyon, Université Claude Bernard Lyon1, INSERM, Stem Cell and Brain Research Institute U1208, 69500 Bron, France; Amsterdam Neuroscience, Cellular and Molecular Mechanisms, Amsterdam, the NetherlandsUniversity Lyon, Université Claude Bernard Lyon1, INSERM, Stem Cell and Brain Research Institute U1208, 69500 Bron, FranceUniversity Lyon, Université Claude Bernard Lyon1, INSERM, Stem Cell and Brain Research Institute U1208, 69500 Bron, France; Corresponding authorSummary: Germinal activity persists throughout life within the ventricular-subventricular zone (V-SVZ) of the postnatal forebrain due to the presence of neural stem cells (NSCs). Accumulating evidence points to a recruitment for these cells following early brain injuries and suggests their amenability to manipulations. We used chronic hypoxia as a rodent model of early brain injury to investigate the reactivation of cortical progenitors at postnatal times. Our results reveal an increased proliferation and production of glutamatergic progenitors within the dorsal V-SVZ. Fate mapping of V-SVZ NSCs demonstrates their contribution to de novo cortical neurogenesis. Transcriptional analysis of glutamatergic progenitors shows parallel changes in methyltransferase 14 (Mettl14) and Wnt/β-catenin signaling. In agreement, manipulations through genetic and pharmacological activation of Mettl14 and the Wnt/β-catenin pathway, respectively, induce neurogenesis and promote newly-formed cell maturation. Finally, labeling of young adult NSCs demonstrates that pharmacological NSC activation has no adverse effects on the reservoir of V-SVZ NSCs and on their germinal activity.http://www.sciencedirect.com/science/article/pii/S2211124724000627CP: NeuroscienceCP: Developmental biology
spellingShingle Louis Foucault
Timothy Capeliez
Diane Angonin
Celia Lentini
Laurent Bezin
Christophe Heinrich
Carlos Parras
Vanessa Donega
Guillaume Marcy
Olivier Raineteau
Neonatal brain injury unravels transcriptional and signaling changes underlying the reactivation of cortical progenitors
Cell Reports
CP: Neuroscience
CP: Developmental biology
title Neonatal brain injury unravels transcriptional and signaling changes underlying the reactivation of cortical progenitors
title_full Neonatal brain injury unravels transcriptional and signaling changes underlying the reactivation of cortical progenitors
title_fullStr Neonatal brain injury unravels transcriptional and signaling changes underlying the reactivation of cortical progenitors
title_full_unstemmed Neonatal brain injury unravels transcriptional and signaling changes underlying the reactivation of cortical progenitors
title_short Neonatal brain injury unravels transcriptional and signaling changes underlying the reactivation of cortical progenitors
title_sort neonatal brain injury unravels transcriptional and signaling changes underlying the reactivation of cortical progenitors
topic CP: Neuroscience
CP: Developmental biology
url http://www.sciencedirect.com/science/article/pii/S2211124724000627
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