Oligodendrocyte Precursor Cell and Oligodendrocyte Markers

What are OPCs?

The definition of OPCs is still in development since their discovery. The existence of OPCs was first suggested by ultrastructural electron microscopy studies between the 1960s and 1970s and was further identified with the discovery of their markers, NG2, PDGFRα, and A2B5, in primary cultures and in vivo. It is now considered that OPCs as neuroectoderm-origin multipotent progenitors that are NG2/PDGFRα positive, highly ramified, mainly generating OLs, but are also capable of giving rise to other CNS cell types including astrocytes.

Markers and Morphology

Various markers have been identified to label OPCs in different developmental states. NG2 and PDGFRα remain the most reliable and widely used markers for OPCs, which could reveal their ramified morphology, a characteristic distinguishing OPCs from NG2-positive pericytes or PDGFRα-positive VLMCs, which display a flat morphology and are lack of processes. In addition, transcription factors NKX2.1 and DLX2 can label early OPCs in the human telencephalon, while O4 labels the non-migratory, late OPCs. In addition, transcription factors NKX2.1 and DLX2 can label early OPCs in the human telencephalon, while O4 labels the non-migratory, late OPCs. 

 The arrival of the single-cell era also provides novel markers for identifying OPCs as well as different stages of oligodendroglial lineage cells. In the developing human brain, single-cell RNA seq identified a transitional cell type lying between multi-potent neural progenitor cells and lineage-committed early OPCs, defined as “pre-OPC”, which possesses expression of both neural progenitor cell markers including GFAP, VIM, NES, HES1, NOTCH2, and EGFR, and oligodendroglial lineage markers OLIG1, OLIG2, and PDGFRα. The same study also identified a potential novel OPC marker PCDH15, which regulates daughter cell separation after division. In addition, differentiation-committed OPCs were also identified, with a unique expression pattern of Tcf7l2, Itpr2, Tmem2, Gpr17, and Pdgfa. Among them, TCF7L2, ITPR2, and GPR17 are adopted as a marker for differentiation-committed OPCs or newly-formed OLs. In addition, activated OPCs in CNS injury highly express Rnf43, which is then downregulated during OL differentiation; RNF43 is thus considered a marker of reactive OPCs.