We first confirmed no difference between control and mutant lines in respect to specification, OPC proliferation, maturation as measured by transition from PDGFRα+‐OPCs to O4+/MBP+‐oligodendrocytes or viability despite the widespread presence of RNA foci. Further pathological characterization revealed an absence of DPRs and TDP‐43 and/or p62 aggregates consistent with the recent pathological findings showing no clear association between the presence of RNA foci and TDP‐43 or p62 aggregation 65. Further interpretation of these findings is challenging as there is, to date, a limited literature describing oligodendrocyte specific pathological findings in ALS. In addition to reduced glial C9ORF72 expression compared with neurons there is well‐documented regional variation in pathology. For instance TDP‐43 and/or p62 inclusions are notably abundant in the cerebella and hippocampi 66, 67, 68. Together with the absence of cytotoxicity this suggests that the presence of the C9ORF72 mutation does not confer detrimental effects on maturation or survival of oligodendrocytes.
