We next investigated the consequence of C9ORF72 mutation on differentiating oligodendrocytes. C9ORF72 hexanucleotide repeat expansion results in reduction of C9ORF72 expression in the brain of patients carrying this mutation 37, 40, 41, 42. Therefore, we examined the expression of the C9ORF72 v2 isoform transcript, the most abundant of the isoforms, and total transcript levels (including isoforms v1, v2, and v3) in mutant oligodendrocytes. We observed no consistent reduction when compared with controls (Fig. 7B). The source of variability in these data may be that the detected C9ORF72 mRNA levels in oligodendrocytes were low when compared with iPSC‐derived neurons (relative fold expression with respect to neurons; v1, 11.0%; v2, 41.7%; v3, 3.9%), in agreement with the finding that C9ORF72 is highly expressed in neurons compared with glia cells 43. Expanded repeats also generate repeat RNA that results in formation of RNA 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
