Transcriptional profiling of isogenic Friedreich ataxia iPSC-derived neurons

Friedreich ataxia (FRDA) is a rare childhood neurodegenerative disorder with no effective treatment. FRDA is caused by the transcriptional silencing of the FXN gene and consequent loss of the essential mitochondrial protein frataxin. We derived a set of isogenic iPSC lines that differ only in the length of the GAA·TCC repeats, using “scarless” gene-editing methods (helper-dependent adenovirus-mediated homologous recombination). To uncover the gene expression signature due to GAA•TCC repeat expansion in FRDA neuronal cells , we performed transcriptomic analysis of iPSC-derived neurons by RNA sequencing. We find that multiple cellular pathways are affected by the loss of frataxin in central nervous system neurons.