Single-cell transcriptome analyses reveal signals to activate dormant neural stem cells

Area of Science:

• Neuroscience
• Stem Cell Biology
• Molecular Biology

Background:

• Characterizing tissue-specific stem cells is challenging due to their scarcity and complex microenvironments.
• Ependymal cells in the adult mouse forebrain neurogenic zone are a potential source of neural stem cells (NSCs).

Purpose of the Study:

• To molecularly characterize quiescent ependymal cells (CD133(+)/GFAP(-)) in the adult mouse forebrain.
• To investigate the activation and differentiation potential of ependymal NSCs.

Main Methods:

• Single-cell transcriptome analysis.
• Weighted gene co-expression network analysis (WGCNA).
• In vivo administration of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF).

Main Results:

• Quiescent ependymal CD133(+)/GFAP(-) cells possess a unique gene network enriched for immune-responsive and angiogenic factor receptor genes.
• VEGF administration activated ependymal NSCs throughout the lateral and fourth ventricles.
• VEGF and bFGF co-administration induced neural lineage differentiation and migration.

Conclusions:

• Dormant ependymal NSCs are present throughout the central nervous system (CNS) ventricular surfaces.
• Immune and angiogenic signals, particularly VEGF, can activate these dormant NSCs, especially after injury.
• This discovery opens new possibilities for brain repair and regeneration strategies.