Second, one may need to consider targeting OL subpopulations. While specific functions of OL subpopulations remain to be elucidated, the shift in OL populations in disease may contribute to pathology and therefore may need to be considered for targeted therapy. For instance, an OL subpopulation with alteration in pathways related to inflammation and lipid metabolism has been found to emerge in several models of demyelination (toxin induced, autoimmune-mediated, and an amyloidosis model of Alzheimer’s disease), identified by high expression of C4b and Serpina3n72,192–194; accordingly, OLs expressing complement have been observed in numerous neurodegenerative diseases. Should this population be associated with increased vulnerability to injury or contribution to myelin pathology, targeting this subpopulation would be of interest. Moreover, the differential responses of the OL lineage in white vs gray matter, particularly in the context of remyelination, suggests the importance of considering distinct regional responses of OLs to therapeutics.
