Cell of all trades: oligodendrocyte precursor cells in synaptic, vascular, and immune function

Abstract

Oligodendrocyte precursor cells (OPCs) are not merely a transitory progenitor cell type, but rather a distinct and heterogeneous population of glia with various functions in the developing and adult central nervous system. In this review, we discuss the fate and function of OPCs in the brain beyond their contribution to myelination. OPCs are electrically sensitive, form synapses with neurons, support blood-brain barrier integrity, and mediate neuroinflammation. We explore how sex and age may influence OPC activity, and we review how OPC dysfunction may play a primary role in numerous neurological and neuropsychiatric diseases. Finally, we highlight areas of future research.

Keywords: Alzheimer's disease; NG2 glia; blood–brain barrier; immunity; neurodevelopment; oligodendrocyte precursor; senescence; sex differences; synapse.

Figure 1.

Transcription factors, growth factors, signaling pathways, and markers of cell identity associated with different stages of oligodendrocyte precursor cell (OPC) maintenance and differentiation. OPC proliferation and self-renewal depend on PDGFα–PDGFRα signaling, high Wnt tone, and PKC activation. Insulin, T₃, and cortisol disinhibit differentiation of OPCs into mature oligodendrocytes (OLs), likely through counteracting PKC activation. OPCs can be induced to differentiate into Type 2 astrocytes by BMPs and IFNγ. Although some evidence suggests that OPCs express proneural transcription factors such as Sox2 and Pax6, and neuronal precursor markers such as doublecortin (DCX), it is unknown whether OPCs give rise to appreciable numbers of neurons in vivo.

Figure 2.

Transcription factors, growth factors, signaling pathways, and markers of cell identity associated with different stages of oligodendrocyte precursor cell (OPC) maintenance and differentiation. OPC proliferation and self-renewal depend on PDGFα–PDGFRα signaling, high Wnt tone, and PKC activation. Insulin, T₃, and cortisol disinhibit differentiation of OPCs into mature oligodendrocytes (OLs), likely through counteracting PKC activation. OPCs can be induced to differentiate into Type 2 astrocytes by BMPs and IFNγ. Although some evidence suggests that OPCs express proneural transcription factors such as Sox2 and Pax6, and neuronal precursor markers such as doublecortin (DCX), it is unknown whether OPCs give rise to appreciable numbers of neurons in vivo.