Cells that express the NG2 chondroitin sulfate proteoglycan and platelet-derived growth factor receptor alpha (NG2 glia) are widespread in the adult human cerebral cortex and white matter and represent 10–15% of non-neuronal cells. The morphology and distribution of NG2 glia are similar to, but distinct from, both microglia and astrocytes. They are present as early as 17 weeks gestation and persist throughout life. NG2 glia can be detected in a variety of human central nervous system (CNS) diseases, of which multiple sclerosis is the best studied. NG2 glia show morphological changes in the presence of pathology and can show expression of the Ki-67 proliferation antigen. The antigenic profile and morphology of NG2 glia in human tissues are consistent with an oligodendrocyte progenitor function that has been well established in rodent models. Most antibodies to NG2 do not stain formalin-fixed paraffin-embedded tissues. Advances in our understanding of NG2 glia in human tissues will require the development of more robust markers for their detection in routinely processed human specimens.

Glial progenitor cells (GPCs) comprise the most abundant population of progenitor cells in the adult human brain. They are responsible for central nervous system (CNS) remyelination, and likely contribute to the astrogliotic response to brain injury and degeneration as well. Adult human GPCs are biased to differentiate as oligodendrocytes and elaborate new myelin, and yet they retain multilineage plasticity, and can give rise to neurons as well as astrocytes and oligodendrocytes once removed from the adult parenchymal environment. GPCs retain strong mechanisms for cell-autonomous self-renewal, and yet both their phenotype and fate may be dictated by their microenvironment. Using the transcriptional profiles of acutely isolated GPCs, we have begun to understand the operative ligand–receptor interactions involved in these processes, and have identified several key signaling pathways by which adult human GPCs may be reliably instructed to either oligodendrocytic or astrocytic fate. In addition, we have noted significant differences between the expressed genes and dominant signaling pathways of fetal and adult human GPCs, as well as between rodent and human GPCs. The latter data in particular call into question therapeutic strategies predicated solely upon data obtained using rodents, while perhaps highlighting the extent to which evolution has been attended by the phylogenetic modification of glial phenotype and function.

Oligodendrocyte precursors (OLPs or ‘NG2 cells’) are abundant in the adult mouse brain, where they continue to proliferate and generate new myelinating oligodendrocytes. By cumulative BrdU labelling, we estimated the cell cycle time TC and the proportion of NG2 cells that is actively cycling (the growth fraction) at ~ postnatal day 6 (P6), P60, P240 and P540. In the corpus callosum, TC increased from <2 days at P6 to ~9 days at P60 to ~70 days at P240 and P540. In the cortex, TC increased from ~2 days to >150 days over the same period. The growth fraction remained relatively invariant at ~50% in both cortex and corpus callosum – that is, similar numbers of mitotically active and inactive NG2 cells co-exist at all ages. Our data imply that a stable population of quiescent NG2 cells appears before the end of the first postnatal week and persists throughout life. The mitotically active population acts as a source of new oligodendrocytes during adulthood, while the biological significance of the quiescent population remains to be determined. We found that the mitotic status of adult NG2 cells is unrelated to their developmental site of origin in the ventral or dorsal telencephalon. We also report that new oligodendrocytes continue to be formed at a slow rate from NG2 cells even after P240 (8 months of age).