What Are the Roles of Oligodendrocyte Precursor Cells in Normal and Pathologic Conditions?

Adult oligodendrocyte precursor (or progenitor) cells (OPCs) are the most proliferative cells in the CNS and constitute approximately 10% of cells in the human brain.1,2 Whereas their primary function is to generate mature myelinating oligodendrocytes,2-4 there is increased evidence that OPCs have multiple myelination-independent functions in the nervous system both in health and disease.5 These cells constitute a heterogeneous population6 and have several unique properties (Figure).4,7-10 As proposed in a recent review,5 OPCs may function as sensors of multiple environmental signals, integrate these signals to subsequently influence surrounding non-neural cells, and bidirectionally interact with axons to regulate circuit maturation and remodeling.5One salient feature of OPCs is that they receive direct synaptic input11; express receptors for several neurotransmitters, including glutamate and gamma-aminobutyric acid (GABA); and express a wide variety of ion channels.12-14 This allows OPCs to precisely detect neuronal activity that regulates their development and differentiation, which is critical for activity-dependent (adaptive) myelination.1,7-10 Reciprocally, OPCs may communicate with surrounding neurons and other cells by releasing several mediators through exocytosis15 or exosomes.16 OPCs have high metabolic demands,17,18 which make them vulnerable to oxidative damage during hypoxia-ischemia.19,20 They function as sensors of hypoxia and promote angiogenesis21 and respond to signals from astrocytes and microglia to contribute to neuroinflammation and glial scar formation.22-24 Oligodendrocyte precursor cells have the potential for remyelination after injury but may have a limited role in human demyelinating disease.25-27 Inability of proliferating OPCs to differentiate into mature oligodendrocytes leads to myelin loss in neurodegenerative disorders.28 Oligodendrocyte precursors are the primary cell type for development of gliomas.29 Thus, OPCs have a fundamental role both in the normal CNS and in a wide spectrum of pathologic conditions. There are recent reviews on the role of OPCs in health and disease,5,30 and only some salient concepts will be emphasized in this paper.