Myc determines the functional age state of oligodendrocyte progenitor cells

Like many adult stem cell populations, the capacity of oligodendrocyte progenitor cells (OPCs) to proliferate and differentiate is significantly impaired with ageing. Previous work has shown that tissue-wide transient expression of the pluripotency factors Oct4, Sox2, Klf4 and c-Myc extends lifespan and enhances somatic cell function. Here we show that just one of these factors, c-Myc, is sufficient to determine the age state of the OPC: c-Myc expression in aged OPCs drives their functional rejuvenation, while inhibition of c-Myc in neonatal OPCs induces an aged-like phenotype, as determined by in vitro assays and transcriptome analysis. We show that increasing c-Myc expression specifically in aged OPCs in vivo restores their proliferation and differentiation capacity, thereby enhancing regeneration in an otherwise aged CNS environment. More generally, our results directly link Myc to cellular activity and cell age-state, with implications for understanding regeneration in the context of ageing and provide important insights into the biology of stem cell ageing.