Regional diversity in oligodendrocyte progenitor cells:implications for remyelination in grey and white matter

Multiple sclerosis (MS) is a chronic disease of the central nervous system in which myelin -an insulating layer around axons- is locally damaged. Myelin can be regenerated by an endogenous process called remyelination, which ultimately fails in MS. Remarkably, remyelination is faster in the grey than in the white matter. For robust remyelination, oligodendrocyte progenitor cells (OPCs) have to maturate into myelinating oligodendrocytes. This study revealed that OPCs from grey matter are better equipped for remyelination than their white matter counterparts. Cultured OPCs from grey matter are less mature, an important prerequisite for the initiation of remyelination. Furthermore, the maturation of grey matter OPCs is less hampered by inflammatory mediators and myelin debris than the maturation of white matter OPCs. The latter may be partially explained by the fact that grey matter OPCs process several environmental signals using a cellular antenna, the primary cilium. White matter OPCs are less receptive to these signals via the primary cilium. A surprising finding is that the characteristic binding of antibody A2B5 to cells directly isolated from brain apparently is not restricted to OPCs. The antibody apparently binds multiple cell types, which differ in the developing and adult brain. While these cell types are not different in the grey and white matter, transcriptomic analysis does indicate functional differences. Altogether, studies investigating the failure of remyelination in MS should take regional differences in OPCs into account. This can potentially lead to regionally differing therapeutic avenues aimed at restoring remyelination in MS