Single-Cell Transcriptome Analyses Reveal Signals to Activate Dormant Neural Stem Cells

The scarcity of tissue-specific stem cells and the complexity of their surrounding environment have made molecular characterization of these cells particularly challenging. Through single-cell transcriptome and weighted gene co-expression network analysis (WGCNA), we uncovered molecular properties of CD133+/GFAP− ependymal (E) cells in the adult mouse forebrain neurogenic zone. Surprisingly, prominent hub genes of the gene network unique to ependymal CD133+/GFAP− quiescent cells were enriched for immune-responsive genes, as well as genes encoding receptors for angiogenic factors. Administration of vascular endothelial growth factor (VEGF) activated CD133+ ependymal neural stem cells (NSCs), lining not only the lateral but also the fourth ventricles and, together with basic fibroblast growth factor (bFGF), elicited subsequent neural lineage differentiation and migration. This study revealed the existence of dormant ependymal NSCs throughout the ventricular surface of the CNS, as well as signals abundant after injury for their activation. [Display omitted] •Single-cell RNA-seq reveals a signature gene program in ependymal CD133+ cells•VEGF is a mitogen for ependymal CD133+ cells and bFGF for subependymal B cells•CD133+ cells lining the fourth ventricle show NSC activity upon VEGF/bFGF treatment Using single-cell transcriptome and network analyses, Luo et al. identify a subset of quiescent neural stem cells in non-neurogenic brain regions and show that these cells could be mitotically activated and differentiated into neurons and glia upon stimulation.