OLs show intrinsic heterogeneity as has recently been demonstrated at the transcriptional level using single cell/nuclei RNA sequencing, with 6–9 subpopulations of OLs identified in mouse and human brain under healthy conditions and in the context of demyelination (EAE and MS)71,72. A significant amount of overlap between human and mouse clusters has been observed. Of interest, mature OL clusters expressing genes suggestive of immune function have been identified, for example supporting an MHC-class II-mediated response71. In this regard, a recent study revealed a human-specific OL subpopulation enriched in the spinal cord with predicted immune function73. Examples of regional differences in OL function include observations that spinal cord OLs form longer myelin sheaths on microfibres than their cortical counterparts, recapitulating in vivo myelin properties74. OLs show faster differentiation yet slower remyelination in white matter vs gray matter in mouse models and MS lesions, and reduced remyelination in spinal cord vs deep white matter75–80. However, white matter OL lineage cells are more intrinsically regulated vs those in the gray matter, as transplantations into the adult mouse cerebral cortex revealed that white matter-derived
