Oligodendrocyte progenitors isolated directly from developing telencephalon at a specific phenotypic stage: myelinogenic potential in a defined environment

Abstract

Oligodendroglia differentiate asynchronously in the developing central nervous system, passing through a series of stages identified by the sequential expression of specific differentiation antigens, culminating in the formation of the myelin sheath. In the work presented here, oligodendrocyte progenitors at a temporally narrow and well-defined phenotypic stage of development have been isolated in high purity and yield directly from postnatal rat telencephalon. This stage is identified by the expression of the O4 antigen, the earliest recognized surface marker specific for the oligodendroglial lineage, but the absence of the differentiation marker galactosylcerebroside (GalC). These O4+ GalC- progenitors first appear at birth (10(5)/telencephalon), 2–3 days before O4+ GalC+ oligodendrocytes. The work presented here demonstrates that a major subpopulation of O4+ GalC- progenitors (80%), which we have termed ‘proligodendrocytes’, is fully committed to terminal oligodendrocyte differentiation. A relatively small, maximal set of nutritional supplements are sufficient for proligodendrocytes to carry out the myelinogenic cascade of differentiated gene expression in a temporally normal manner, in quantitatively significant amounts, in normal ratios of myelin protein isoforms, and in a regulated relationship to the inclusion of myelin-specific products into myelin-like membrane sheets. An important corollary is that this step of myelinogenesis does not require contact with other cell types, in particular neurones and astrocytes, nor does it require unknown growth factors unique to these cell types. Additionally under these conditions, there exists a developmentally quiescent subpopulation (20%) of O4+ GalC- cells that may have significance for understanding the progenitors previously described in adult brain and suggested to be instrumental in remyelination under pathological conditions.