Sox2 sustains recruitment of oligodendrocyte progenitor cells following CNS demyelination and primes them for differentiation during CNS remyelination
Fancy, Stephen PJ
de, Castro Glaucia M
Journal of Neuroscience
Society for Neuroscience
MetadataShow full item record
Zhao, C., Ma, D., Zawadzka, M., Fancy, S. P., Elis-Williams, L., Bouvier, G., Stockley, J., et al. (2015). Sox2 sustains recruitment of oligodendrocyte progenitor cells following CNS demyelination and primes them for differentiation during CNS remyelination. Journal of Neuroscience, 35 11482-11499. https://doi.org/10.1523/JNEUROSCI.3655-14.2015
The Sox family of transcription factors have been widely studied in the context of oligodendrocyte development. However, comparatively little is known about the role of Sox2, especially during CNS remyelination. Here we show that expression of Sox2 occurs in oligodendrocyte progenitor cells (OPCs) in rodent models during myelination and in activated adult OPCs responding to demyelination, and is also detected in MS lesions. In normal adult white matter in both mice and rats it is neither expressed by adult OPCs nor by oligodendrocytes (although it is expressed by a sub-population of adult astrocytes). Overexpression of Sox2 in rat OPCs in vitro maintains the cells in a proliferative state and inhibits differentiation, while Sox2 knock out results in decreased OPC proliferation and survival, suggesting that Sox2 contributes to the expansion of OPCs during the recruitment phase of remyelination. Loss-of-function in cultured mouse OPCs also results in an impaired ability to undergo normal differentiation in response to differentiation signals, suggesting that Sox2 expression in activated OPCs also primes these cells to eventually undergo differentiation. In vivo studies on remyelination following experimental toxin-induced demyelination in mice with inducible loss of Sox2 revealed impaired remyelination, which was largely due to a profound attenuation of OPC recruitment and likely also due to impaired differentiation. Our results reveal a key role of Sox2 expression in OPCs responding to demyelination, enabling them to effectively contribute to remyelination.
demyelination, remyelination, Sox2, oligodendrocyte progenitor cells
This work was mainly supported by the UK Multiple Sclerosis Society.
External DOI: https://doi.org/10.1523/JNEUROSCI.3655-14.2015
This record's URL: https://www.repository.cam.ac.uk/handle/1810/248973
Attribution 2.0 UK: England & Wales
Licence URL: http://creativecommons.org/licenses/by/2.0/uk/
Recommended or similar items
The following licence files are associated with this item: