Multipotent neural stem cells originating from neuroepithelium exist outside of the mouse central nervous system [scRNA-seq]

It has been widely accepted that mammalian neural stem cells (NSCs) exist only in the central nervous system. Here, we report that peripheral NSCs (pNSCs) exist outside of the CNS and can be isolated—from mouse embryonic limb, postnatal lung, tail, dorsal root ganglia, and adult lung tissues. Derived pNSCs are distinguished from neural crest stem cells, express multiple NSC-specific markers and exhibit cell morphology, self-renewing capacity, genome-wide transcriptional profile, epigenetic features, and differentiation ability similar to those of control brain NSCs. pNSCs are from Sox1+ cells and originate from neuroepithelial cells. Single-cell RNA sequencing identifies that pNSCs in situ show similar molecular feature to brain NSCs. Furthermore, many pNSCs that migrate out of the neural tube can differentiate into neurons and limited glia cells during embryo development. Our finding of the existence of pNSCs provides previously unidentified insight of the mammalian nervous system development and presents an alternative potential strategy for neural regenerative therapy. Overall design: Single cell RNA sequencing of Sox2-GFP+ lung cells, Sox1-GFP+ brain cells and Sox1-GFP+ tail cells