Oct 30, 2018

Transcriptional profiling of isogenic Friedreich ataxia induced pluripotent stem cell-derived neurons

BioRxiv : the Preprint Server for Biology
Jiun-I LaiElisabetta Soragni


Friedreich ataxia (FRDA) is a rare childhood neurodegenerative disorder with no effective treatment. FRDA is caused by transcriptional silencing of the FXN gene and consequent loss of the essential mitochondrial protein frataxin. Based on the knowledge that a GAA·TTC repeat expansion in the first intron of FXN leads to heterochromatin formation and gene silencing, we have shown that members of the 2-aminobenzamide family of histone deacetylase inhibitors (HDACi) reproducibly increase FXN mRNA levels in induced pluripotent stem cell (iPSC)-derived FRDA neuronal cells and in peripheral blood mononuclear cells from patients treated with the drug in a phase I clinical trial. How the reduced expression of frataxin leads to neurological and other systemic symptoms in FRDA patients remains unclear. Similarly to other triplet repeat disorders, it is not known why only specific cells types are affected in the disease, primarily the large sensory neurons of the dorsal root ganglia and cardiomyocytes. The combination of iPSC technology and genome editing techniques offers the unique possibility of addressing these questions in a relevant cell model of the disease, without the confounding effect of different genetic backgrounds. We derived...Continue Reading

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Mentioned in this Paper

Biochemical Pathway
Mononuclear Cells
Pluripotent Stem Cells
Heterochromatin Assembly
Peripheral Blood
Gene Editing
Sequence Determinations, RNA
Peripheral Blood Mononuclear Cells (Lab Test)
Transcription, Genetic

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