RNA sequencing revealed a distinct transcriptional profile associated with frataxin deficiency. MEG3 and PCDHGA10 were consistently dysregulated across all three FRDA-iPSC lines and may represent early molecular markers of FRDA cardiomyopathy. Functional interrogation of these candidates demonstrated that targeted silencing of MEG3 or PCDHGA10 in FRDA cardiomyocytes significantly reduced disease‑associated cell death without affecting FXN expression. Notably, PCDHGA10 silencing also normalized elevated mitochondrial reactive oxygen species, whereas MEG3 silencing did not, highlighting gene‑specific contributions to FRDA cardiomyocyte survival. Collectively, these findings identify MEG3 and PCDHGA10 as functionally relevant regulators of FRDA cardiomyocyte pathology.
Tuesday, June 23, 2026
Frataxin deficiency drives cardiac dysfunction and transcriptional dysregulation in Friedreich ataxia iPSC model
Lees, J.G., Zhang, H., Jiao, L. et al. Frataxin deficiency drives cardiac dysfunction and transcriptional dysregulation in Friedreich ataxia iPSC model. Cell Death Dis (2026). doi:10.1038/s41419-026-09030-3
