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Article

Cardiomyocytes Derived from Induced Pluripotent Stem Cells as a Disease Model for Propionic Acidemia

by 1,2,3,4, 1,2,3,4, 1,2,3,4 and 1,2,3,4,*
1
Centro de Biología Molecular Severo Ochoa UAM-CSIC, Universidad Autónoma de Madrid, 28049 Madrid, Spain
2
Centro de Diagnóstico de Enfermedades Moleculares (CEDEM), 28049 Madrid, Spain
3
Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), ISCIII, 28029 Madrid, Spain
4
Instituto de Investigación Sanitaria Hospital La Paz (IdiPaz), ISCIII, 28029 Madrid, Spain
*
Author to whom correspondence should be addressed.
Academic Editor: Rivka Ofir
Int. J. Mol. Sci. 2021, 22(3), 1161; https://doi.org/10.3390/ijms22031161
Received: 30 December 2020 / Revised: 20 January 2021 / Accepted: 21 January 2021 / Published: 25 January 2021
(This article belongs to the Special Issue hiPSC-Derived Cells as Models for Drug Discovery)
Propionic acidemia (PA), one of the most frequent life-threatening organic acidemias, is caused by mutations in either the PCCA or PCCB genes encoding both subunits of the mitochondrial propionyl-CoA carboxylase (PCC) enzyme. Cardiac alterations (hypertrophy, dilated cardiomyopathy, long QT) are one of the major causes of mortality in patients surviving the neonatal period. To overcome limitations of current cellular models of PA, we generated induced pluripotent stem cells (iPSCs) from a PA patient with defects in the PCCA gene, and successfully differentiated them into cardiomyocytes. PCCA iPSC-derived cardiomyocytes exhibited reduced oxygen consumption, an accumulation of residual bodies and lipid droplets, and increased ribosomal biogenesis. Furthermore, we found increased protein levels of HERP, GRP78, GRP75, SIG-1R and MFN2, suggesting endoplasmic reticulum stress and calcium perturbations in these cells. We also analyzed a series of heart-enriched miRNAs previously found deregulated in the heart tissue of a PA murine model and confirmed their altered expression. Our novel results show that PA iPSC-cardiomyocytes represent a promising model for investigating the pathological mechanisms underlying PA cardiomyopathies, also serving as an ex vivo platform for therapeutic evaluation. View Full-Text
Keywords: propionic acidemia; cardiac dysfunction; iPSC; iPSC-derived cardiomyocytes; disease model propionic acidemia; cardiac dysfunction; iPSC; iPSC-derived cardiomyocytes; disease model
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MDPI and ACS Style

Alonso-Barroso, E.; Pérez, B.; Desviat, L.R.; Richard, E. Cardiomyocytes Derived from Induced Pluripotent Stem Cells as a Disease Model for Propionic Acidemia. Int. J. Mol. Sci. 2021, 22, 1161. https://doi.org/10.3390/ijms22031161

AMA Style

Alonso-Barroso E, Pérez B, Desviat LR, Richard E. Cardiomyocytes Derived from Induced Pluripotent Stem Cells as a Disease Model for Propionic Acidemia. International Journal of Molecular Sciences. 2021; 22(3):1161. https://doi.org/10.3390/ijms22031161

Chicago/Turabian Style

Alonso-Barroso, Esmeralda, Belén Pérez, Lourdes R. Desviat, and Eva Richard. 2021. "Cardiomyocytes Derived from Induced Pluripotent Stem Cells as a Disease Model for Propionic Acidemia" International Journal of Molecular Sciences 22, no. 3: 1161. https://doi.org/10.3390/ijms22031161

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