Supporting Data for "Multipotent neural stem cells are found in the mouse periphery and contribute to early peripheral neural development"

Through extensive immunostaining and single-cell sequencing of near-term embryonic tissues, we demonstrate that pNSC progeny contribute to multiple peripheral cell populations, including neurons and a smaller fraction of glial cells, across diverse tissues. Postnatal mapping further revealed marked tissue- and region-specific differences in pNSC persistence. In most peripheral tissues, pNSCs were detected only transiently and declined rapidly after birth, whereas the lung retained Sox1-positive pNSC clusters from neonatal stages into adulthood, identifying it as a uniquely stable peripheral niche for long-term pNSC maintenance.

Upon bronchial injury, lung pNSCs exhibited limited Ki67 expression and gave rise to Sox1-negative, non-neuronal progeny, suggesting a restricted regenerative response in the endogenous lung niche.</p><p dir="ltr">Functional analyses further showed that peripheral tissue-derived pNSCs can be expanded in vitro for extended periods and are capable of differentiation into neurons, astrocytes, and oligodendrocytes, confirming their multipotency.</p><p dir="ltr">Collectively, these findings establish pNSCs as a neuroepithelium-derived stem cell population with broad peripheral distribution during development, tissue-dependent postnatal persistence, and context-dependent responses to injury in the lung.

Our findings expand current understanding of mammalian NSC development and offer a more accessible source of endogenous NSCs with potential relevance to regenerative medicine.</p>