Heterogeneity of Oligodendrocytes and Their Precursor Cells

While oligodendrocytes have been thought to be homogenous, a number of reports have indicated evidences of the heterogeneity of oligodendrocytes and their precursor cells, OPCs. Almost a century ago, Del Río Hortega found three and four types of oligodendrocytes with regions where they exist and their morphologies, respectively. Interfascicular oligodendrocytes are one of the three regional dependent types and are the most typical oligodendendroglial cells that myelinate axonal fibers in the white matter tracts. In the other two, perineuronal oligodendrocyes function as reserve cells for remyelination and regulate neuronal excitability, whereas perivascular oligodendrocytes may play a role in metabolic support of axons. Among the four morphological categories, type I and II oligodendrocytes form many myelin sheaths on small-diameter axons and specific signal is required for the myelination of small-diameter axons. Type III and IV oligodendrocytes myelinate a few number of axons/or one axon, whose diameters are large. A recent comprehensive gene expression analysis with single-cell RNA sequencing identifies six different populations in mature oligodendrocytes and only one population in OPCs. However, OPCs are not uniformed developmentally and regionally. Further, the capacity of OPC differentiation depends on the environments and conditions of the tissues. Taken together, oligodendrocytes and OPCs are diverse as the other cell types in the CNS. The orchestration of these cells with their specialized functions is critical for proper functioning of the CNS.