Abstract
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.
Original language | English |
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Article number | 113734 |
Pages (from-to) | 113734 |
Journal | Cell reports |
Volume | 43 |
Issue number | 2 |
Early online date | 12 Feb 2024 |
DOIs | |
Publication status | Published - 27 Feb 2024 |
Keywords
- CP: Developmental biology
- CP: Neuroscience
- brain development
- gliogenesis
- glutamatergic progenitors
- neonatal brain injury
- neural stem cells
- neurogenesis
- pharmacological treatment
- ventricular-subventricular zone