Recent advances in deciphering oligodendrocyte heterogeneity with single-cell transcriptomics

Oligodendrocytes (OL) have been for decades considered a passive, homogenous population of cells that provide support to neurons, and show a limited response to pathological stimuli. This view has been dramatically changed by the introduction of powerful transcriptomic methods that have uncovered a broad spectrum of OL populations that co-exist within the healthy central nervous system (CNS) and also across a variety of diseases. Specifically, single-cell and single-nucleus RNA-sequencing (scRNA-seq, snRNA-seq) have been used to reveal OL variations in maturation, myelination and immune status. The newly discovered immunomodulatory role suggests that OL may serve as targets for future therapies. In this review, we summarize the current understanding of OL heterogeneity in mammalian CNS as revealed by scRNA-seq and snRNA-seq. We provide a list of key studies that identify consensus marker genes defining the currently known OL populations. This resource can be used to standardize analysis of OL related datasets and improve their interpretation, ultimately leading to a better understanding of OL functions in health and disease.