Specific oligodendrocyte populations have differential spatial distribution and susceptibility to injury

Oligodendrocytes (OLs), the myelinating cells of the central nervous system, are transcriptionally heterogeneous, the origin and functional consequences of which are unknown. We report that mature OL2 (MOL2) preferentially distribute in the spinal cord white matter, while MOL5/6 are abundant in the brain and spinal cord grey matter. Remarkably, MOL2 and MOL5/6 segregate around sensory and motor tracts in the spinal cord, respectively. Lineage tracing, single-cell RNA-Sequencing and RNAscope ISH indicated that the developmental origin does not specify OL progenitors into MOL populations. Following spinal cord injury, we observed depletion of MOL2, while MOL5/6 abundantly repopulate the injury site. Thus, specific MOL populations, identified by scRNAseq, have spatial preference and differential responses to disease, suggesting that OLs are both transcriptionally and functionally heterogeneous.