PUBLICATION
Notch signaling blockade links transcriptome heterogeneity in quiescent neural stem cells with reactivation routes and potential
- Authors
- Morizet, D., Foucher, I., Mignerey, I., Alunni, A., Bally-Cuif, L.
- ID
- ZDB-PUB-250828-10
- Date
- 2025
- Source
- Science advances 11: eadu3189eadu3189 (Journal)
- Registered Authors
- Alunni, Alessandro, Bally-Cuif, Laure, Foucher, Isabelle, Mignerey, Ilona, Morizet, David
- Keywords
- none
- MeSH Terms
-
- Animals
- Astrocytes/cytology
- Astrocytes/metabolism
- Gene Expression Profiling
- Neural Stem Cells*/cytology
- Neural Stem Cells*/metabolism
- Receptors, Notch*/antagonists & inhibitors
- Receptors, Notch*/genetics
- Receptors, Notch*/metabolism
- Signal Transduction*
- Single-Cell Analysis
- Telencephalon/cytology
- Telencephalon/metabolism
- Transcriptome*
- Zebrafish/genetics
- Zebrafish Proteins/genetics
- Zebrafish Proteins/metabolism
- PubMed
- 40864701 Full text @ Sci Adv
Citation
Morizet, D., Foucher, I., Mignerey, I., Alunni, A., Bally-Cuif, L. (2025) Notch signaling blockade links transcriptome heterogeneity in quiescent neural stem cells with reactivation routes and potential. Science advances. 11:eadu3189eadu3189.
Abstract
In the vertebrate brain, neural stem cell (NSC) quiescence is necessary for stemness maintenance. Using single-cell RNA sequencing (scRNAseq) in the zebrafish adult telencephalon, we identified different molecular clusters of quiescent NSCs, interpreted to sign different quiescence depths. Here, we show that these clusters, when challenged in vivo with an inhibitor of Notch signaling, a major quiescence promoting pathway, unfold different behaviors. Notably, deeply quiescent NSCs with astrocytic features display a unique activation phenotype that combines the maintenance of astrocytic markers with the rapid up-regulation of activation and neuronal commitment genes, reminiscent to murine periventricular astrocytes activating upon lesion. In contrast, an NSC cluster predicted to be in the deepest quiescence state resists Notch blockade, and we demonstrate that the transcription factor Nr2f1b mediates this resistance to activation in vivo. These results together link the molecular heterogeneity of quiescent NSCs with bona fide biological properties and their molecular regulators.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping