Prospective identification and characterization of multipotent peripheral neural stem cells out of mammalian central nervous system

It has been widely accepted that mammalian neural stem cells (NSCs) only exist in central nervous system (CNS). Here, we challenge this concept and show that peripheral NSCs (pNSCs) could be isolated out of CNS from mouse embryonic limbs, postnatal tail and adult lung tissues. Derived-pNSCs express multiple NSC-specific markers, exhibit cell morphology, self-renewing capacity, genome-wide transcriptional profile, epigenetic features similar to those of brain control NSCs. Derived-pNSCs can differentiate into astrocytes, electrophysiologically functional neurons, and oligodendrocytes in vitro and in vivo, indicating multipotency. Lineage-tracing results reveal that pNSCs are progeny cells of neural epithelial cells, but not neural crest cells. Furthermore, single cell RNA-seq results identify a unique molecular feature of in vivo pNSCs which express NSCs and oligodendroglial markers. Our finding of pNSCs out of CNS expands the field of developmental neuroscience and presents an alternative potential strategy for neural regenerative therapy. Single cell RNA sequence of andult mouse brain and lung Nestin-GFP+ cells