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.

© 2025. The Author(s).

传统的观点认为哺乳动物的神经干细胞（NSCs）仅存在于中枢神经系统中。在这里，我们报告在外周组织中存在外周神经干细胞（pNSCs），这些细胞可以从小鼠胚胎肢体、出生后的肺部、尾巴、背根神经节和成年肺组织中分离出来。衍生出的pNSCs与神经嵴干细胞不同，表达多种特异性的NSC标志物，并且在细胞形态、自我更新能力、分化潜能、全基因组转录谱及表观遗传特征方面类似于对照大脑中的NSCs。pNSCs由源自神经上皮细胞的Sox1阳性细胞组成，在原位时具有与脑中NSC相似的分子特性。此外，许多从神经管迁移到外周组织的pNSCs在胚胎和出生后的发育过程中可以分化为成熟的神经元和有限的胶质细胞。我们发现pNSCs为哺乳动物神经系统的发展提供了以前未被识别的认识，并且为神经再生治疗提供了一种潜在的新策略。

© 2025. The Author(s).