foci, characteristic of C9ORF72 pathology 37, 44, 45, 46. Using FISH, we observed that iPSC9‐derived O4+‐oligodendrocytes contain nuclear RNA foci (Fig. 7C, 7D). Foci were not observed in control O4+‐oligodendrocytes. In contrast we did not identify dipeptide repeat (DPR) proteins generated by non‐ATG translation of repeat RNA nor did we observe differences in TDP‐43 or p62 subcellular localization in C9ORF72 O4+‐oligodendrocytes (data not shown). In view of recent findings suggesting morphological abnormalities in differentiating oligodendrocytes in mSOD1 experimental and pathological studies 3, we undertook Sholl analysis of week 1 oligodendrocytes, but this did not reveal any difference (data not shown). We address whether the mutation resulted in a cell viability phenotype by undertaking quantitative caspase3/7 counts in O4+‐cells using FACS and no difference was found between mutant and control (p > 0.38; Fig. 7E). Finally, noting that the oligodendrocyte‐specific lactate transporter monocarboxylate transporter‐1 (MCT1) has been described previously to be downregulated in post‐mortem samples of ALS patients and an ALS mouse model 3, 4, 5. Comparisons of MCT1 mRNA expression by qPCR in C9ORF72 mutants with control week 3 oligodendrocytes also did not reveal a difference (p > 0.22, Fig. 7F).
