Oligodendrocyte progenitor cells (OPCs), also known as oligodendrocyte precursor cells, NG2-glia, O2A cells, or polydendrocytes, are a subtype of glia in the central nervous system named for their essential role as precursors to oligodendrocytes and myelin. They are typically identified in the human by co-expression of PDGFRA and CSPG4.

OPCs play a critical role in developmental and adult myelinogenesis. They give rise to oligodendrocytes, which then wrap around axons and provide electrical insulation by forming a myelin sheath. This enables faster action potential propagation and high fidelity transmission without a need for an increase in axonal diameter. The loss or lack of OPCs, and consequent lack of differentiated oligodendrocytes, is associated with a loss of myelination and subsequent impairment of neurological functions. In addition, OPCs express receptors for various neurotransmitters and undergo membrane depolarization when they receive synaptic inputs from neurons.

OPCs are glial cells that are typically identified by co-expression of NG2 (a chondroitin sulfate proteoglycan encoded by CSPG4 in humans) and platelet-derived growth factor receptor alpha (encoded by PDGFRA). They are smaller than neurons, of comparable size to other glia, and can either have a bipolar or complex multipolar morphology with processes reaching up to ~50 μm. OPCs comprise approximately 3–4% of cells in grey matter and 8–9% in white matter, making them the fourth largest group of glia after astrocytes, microglia and oligodendrocytes.

OPCs are present throughout the brain, including the hippocampus and in all layers of the neocortex. They distribute themselves and achieve a relatively even distribution through active self-repulsion. OPCs constantly survey their surroundings through actively extending and retracting processes that have been termed growth cone like processes. Death or differentiation of an OPC is rapidly followed by migration or local proliferation of a neighboring cell to replace it.

In white matter, OPCs are found along unmyelinated axons as well as along myelinated axons, engulfing nodes of Ranvier. Recently, OPCs have been shown to reside in close contact with NG2-expressing pericytes in cerebral white matter, as well.

OPCs receive synaptic contacts onto their processes from both glutamatergic and GABAergic neurons. OPCs receive preferred somatic contacts from fast-spiking GABAergic neurons, while non-fast spiking interneurons have a preference for contacting the processes. These inhibitory connections (in mice) occur mainly during a specific period in development, from postnatal day 8 till postnatal day 13.

OPCs first appear during embryonic organogenesis. In the developing neural tube, Shh (Sonic hedgehog) signaling and expression of Nkx6.1/Nkx6.2 coordinate expression of Olig1 and Olig2 in neuroepithelial cells of the pMN and p3 domains of the ventral ventricular zone. Together, Nkx2.2 and Olig1/Olig2 drive OPC specification.

In the forebrain, three regionally distinct sources have been shown to generate OPCs sequentially. OPCs first originate from Nkx2.1-expressing cells in the ventricular zone of the medial ganglionic eminence. Some OPCs are also generated from multipotent progenitors in the subventricular zone (SVZ). These cells migrate into the olfactory bulb. Depending on their origin in the SVZ, these progenitors give rise to either OPCs or astrocytes. Typically, cells originating from the posterior and dorsomedial SVZ produce more oligodendrocytes owing to increased exposure to posterior Shh signaling and dorsal Wnt signaling which favors OPC specification, in contrast to ventral Bmp signaling which inhibits it.