Proliferation is a requirement for differentiation of oligodendrocyte progenitor cells during CNS remyelination

Oligodendrocytes that generate new myelin sheaths around demyelinated axons in the regenerative process of remyelination are generally derived from oligodendrocyte progenitor cells (OPCs). During this process, OPCs become activated, populate the area of myelin loss, and finally differentiate. Although much is known about the individual stages of remyelination, the exact sequence of events and whether a dependency of each individual stage on each other exists is unknown. Understanding the biology behind these questions is important for the development of remyelination therapies to overcome the age-related decline in remyelination efficiency observed in the chronic phase of multiple sclerosis (MS). Here we show that, following toxin-induced demyelination, all re-populating OPCs first migrate into the site of damage, undergo relatively few rounds of division and eventually differentiate. We further show that OPC proliferation is a requirement for differentiation. Together, our results reveal an unexpected link between OPC proliferation and differentiation, and opens up the possibility of novel regenerative strategies in MS focussing on stimulating OPC proliferation.