Multipotent neural stem cells originating from neuroepithelium exist outside the mouse central nervous system.

Conventional understanding dictates that mammalian neural stem cells (NSCs) exist only in the central nervous system. Here, we report that peripheral NSCs (pNSCs) exist outside the central nervous system and can be isolated from mouse embryonic limb, postnatal lung, tail, dorsal root ganglia and adult lung tissues. Derived pNSCs are distinct from neural crest stem cells, express multiple NSC-specific markers and exhibit cell morphology, self-renewing and differentiation capacity, genome-wide transcriptional profile and epigenetic features similar to control brain NSCs. pNSCs are composed of Sox1(+) cells originating from neuroepithelial cells. pNSCs in situ have similar molecular features to NSCs in the brain. Furthermore, many pNSCs that migrate out of the neural tube can differentiate into mature neurons and limited glial cells during embryonic and postnatal development. Our discovery of pNSCs provides previously unidentified insight into the mammalian nervous system development and presents an alternative potential strategy for neural regenerative therapy.