{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,10]],"date-time":"2026-11-10T21:29:19Z","timestamp":1794346159918,"version":"4.9.0"},"reference-count":68,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2022,11,11]],"date-time":"2022-11-11T00:00:00Z","timestamp":1668124800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molec Gen &amp; Gen Med"],"published-print":{"date-parts":[[2023,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>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 <jats:italic>FXN<\/jats:italic> 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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>To investigate, we generated iPSC\u2010derived neurons (iNs) and cardiomyocytes (iCMs) from an FRDA patient and upregulated <jats:italic>FXN<\/jats:italic> expression via lentivirus without altering genomic GAA repeats at the <jats:italic>FXN<\/jats:italic> locus.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>RNA\u2010seq 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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>These results offer novel insight into specific roles of frataxin deficiency pathogenesis in neurons and cardiomyocytes.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mgg3.2093","type":"journal-article","created":{"date-parts":[[2022,11,12]],"date-time":"2022-11-12T07:21:59Z","timestamp":1668237719000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Frataxin deficiency alters gene expression in Friedreich ataxia derived IPSC\u2010neurons and cardiomyocytes"],"prefix":"10.1002","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1982-8102","authenticated-orcid":false,"given":"Mariana B.","family":"Angulo","sequence":"first","affiliation":[{"name":"Heart Institute, Morsani College of Medicine, University of South Florida  Tampa Florida USA"},{"name":"Department of Molecular Pharmacology &amp; 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