In the context of human neurodegenerative diseases such as MS and Alzheimer’s disease (AD), OLs undergo a shift in gene expression and subpopulations compared to healthy controls71,82,83. Single RNA sequencing of the most extensive MS cohort to date revealed differences in OL heterogeneity in white matter vs gray matter, and vulnerability of a specific OL subpopulation84. OL subpopulation profiles allowed for the stratification of MS samples into 3 types: (1) having OL subpopulations largely similar to that observed in normal appearing white matter, (2) showing an increase in an OL subpopulation with a stressed profile, and (3) indicating a block in OL differentiation84. Of note, pathway analysis of OLs in MS gray and white matter lesions indicated engagement of pathways which include those related to injury responses (e.g., p53 and metabolism)84,85.
