A newly-recognized population of residual neural crest cells in the adult leptomeninges is re-activated for vascular repair

Nakamura, Y.; Nakano, T.; Park, J.-H.; Tanaka, M.; Li, W.; Esposito, E.; Ahn, B.-J.; Duran-Laforet, V.; Desai, R.; Sencan, I.; Sakadzic, S.; Lo, E.; Snyder, E.; Tabaka, M.; Hayakawa, K.

doi:10.1101/2022.12.30.522316

bioRxiv · 10.1101/2022.12.30.522316

A newly-recognized population of residual neural crest cells in the adult leptomeninges is re-activated for vascular repair

Nakamura, Y.·Nakano, T.·Park, J.-H.·Tanaka, M.·Li, W.·Esposito, E.·Ahn, B.-J.·Duran-Laforet, V.·Desai, R.·Sencan, I.·Sakadzic, S.·Lo, E.·Snyder, E.·Tabaka, M.·Hayakawa, K.

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Abstract

The neural crest (NC) is a transient structure in vertebrate embryogenesis comprising highly migratory multipotent stem cells that give rise to a diverse array of cell types in organs throughout the body, including initiating neurovascular patterning. It is assumed that neural crest stem cells (NCSCs) disappear after development. Unexpectedly, using single-nucleus RNA-sequencing, we discovered residual quiescent NCSCs in the adult mouse meninges which are activated by injury and contribute to the brains homeostatic response. RNA velocity, pathway, and transcription factor analyses in a murine stroke model (combined with in vivo imaging) show that these adult NCSCs migrate towards the perivascular spaces of the infarct and undergo a perivascular stromal cell transition that is regulated by Ptp1b, Ghr, and Stat3. Loss- and gain-of-function experiments show that these "vestigial" NCSCs are required for restoring vascular endothelial barrier function via {beta}-catenin and Stat3 signaling. These findings suggest that, in the adult, an unexpected reservoir of cells -- once pivotal to embryogenesis and vascular morphogenesis -- are re-invoked for neurovascular repair.

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Nakamura, Y., Nakano, T., Park, J.-H., Tanaka, M., Li, W., Esposito, E., Ahn, B.-J., Duran-Laforet, V., Desai, R., Sencan, I., Sakadzic, S., Lo, E., Snyder, E., Tabaka, M., Hayakawa, K.. 2022-12-31. A newly-recognized population of residual neural crest cells in the adult leptomeninges is re-activated for vascular repair. https://doi.org/10.1101/2022.12.30.522316

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