Bibliographic Details
| Title: |
Frataxin deficiency alters gene expression in Friedreich ataxia derived IPSC‐neurons and cardiomyocytes |
| Authors: |
Mariana B. Angulo, Alexander Bertalovitz, Mariana A. Argenziano, Jiajia Yang, Aarti Patel, Theresa Zesiewicz, Thomas V. McDonald |
| Source: |
Molecular Genetics & Genomic Medicine, Vol 11, Iss 1, Pp n/a-n/a (2023) |
| Publisher Information: |
Wiley, 2023. |
| Publication Year: |
2023 |
| Collection: |
LCC:Genetics |
| Subject Terms: |
extracellular matrix, frataxin, Friedreich's ataxia, glycolysis, lentivirus, Genetics, QH426-470 |
| More Details: |
Abstract Background Friedreich's ataxia (FRDA) is an autosomal recessive disease, whereby homozygous inheritance of an expanded GAA trinucleotide repeat expansion in the first intron of the FXN gene leads to transcriptional repression of the encoded protein frataxin. FRDA is a progressive neurodegenerative disorder, but the primary cause of death is heart disease which occurs in 60% of the patients. Several functions of frataxin have been proposed, but none of them fully explain why its deficiency causes the FRDA phenotypes nor why the most affected cell types are neurons and cardiomyocytes. Methods To investigate, we generated iPSC‐derived neurons (iNs) and cardiomyocytes (iCMs) from an FRDA patient and upregulated FXN expression via lentivirus without altering genomic GAA repeats at the FXN locus. Results RNA‐seq and differential gene expression enrichment analyses demonstrated that frataxin deficiency affected the expression of glycolytic pathway genes in neurons and extracellular matrix pathway genes in cardiomyocytes. Genes in these pathways were differentially expressed when compared to a control and restored to control levels when FRDA cells were supplemented with frataxin. Conclusions These results offer novel insight into specific roles of frataxin deficiency pathogenesis in neurons and cardiomyocytes. |
| Document Type: |
article |
| File Description: |
electronic resource |
| Language: |
English |
| ISSN: |
2324-9269 |
| Relation: |
https://doaj.org/toc/2324-9269 |
| DOI: |
10.1002/mgg3.2093 |
| Access URL: |
https://doaj.org/article/f794ec56edff47938221c71b1ce133d7 |
| Accession Number: |
edsdoj.f794ec56edff47938221c71b1ce133d7 |
| Database: |
Directory of Open Access Journals |
