Peripheral nerves are highly regenerative in contrast to the poor regenerative capabilities of the CNS. Here we show that adult peripheral nerve is a more quiescent tissue than the CNS, yet all cell-types within a peripheral nerve proliferate efficiently following injury. Moreover, whereas oligodendrocytes are produced throughout life from a precursor pool, we find that the corresponding cell of the PNS, the myelinating Schwann cell (mSC) does not turnover in the adult. However, following injury, all mSCs can dedifferentiate to the proliferating progenitor-like SCs that orchestrate the regenerative response. Lineage analysis shows these newly-migratory, progenitor-like cells redifferentiate to form new tissue at the injury site, maintain their lineage but can switch to become a non-myelinating SC. In contrast, increased plasticity is observed during tumourigenesis. These findings show that peripheral nerves have a distinct mechanism for maintaining homeostasis and can regenerate without the need for an additional stem cell population.

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