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

© 2021 by the authors

Detalles Bibliográficos
Autores: Alonso-Barroso, Esmeralda, Pérez, Belén, Ruiz Desviat, Lourdes, Richard, Eva
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2021
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/227955
Acceso en línea:http://hdl.handle.net/10261/227955
Access Level:acceso abierto
Palabra clave:Propionic acidemia
Cardiac dysfunction
iPSC
iPSC-derived cardiomyocytes
Disease model
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spelling Cardiomyocytes Derived from Induced Pluripotent Stem Cells as a Disease Model for Propionic AcidemiaAlonso-Barroso, EsmeraldaPérez, BelénRuiz Desviat, LourdesRichard, EvaPropionic acidemiaCardiac dysfunctioniPSCiPSC-derived cardiomyocytesDisease model© 2021 by the authorsPropionic 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.Research reported in this work was funded by Grant PAF107 from the Propionic Acidemia Foundation; SAF2016-76004-R from Spanish Ministry of Economy, Industry and Competitiveness— Agencia Estatal de Investigación and European Regional Development Fund (Fondos Feder); PID2019- 105344RB-I00/AEI/10.13039/501100011033 from Spanish Ministry of Science and Innovation and by LCF/PR/PR16/11110018 from Fundación Isabel Gemio, Fundación La Caixa.Peer reviewedMultidisciplinary Digital Publishing InstituteMinisterio de Ciencia, Innovación y Universidades (España)Agencia Estatal de Investigación (España)Fundación Isabel GemioLa CaixaConsejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]2021202120212021info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Publisher's versioninfo:eu-repo/semantics/publishedVersionhttp://hdl.handle.net/10261/227955reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Inglés#PLACEHOLDER_PARENT_METADATA_VALUE##PLACEHOLDER_PARENT_METADATA_VALUE##PLACEHOLDER_PARENT_METADATA_VALUE#info:eu-repo/grantAgreement/MINECO/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016/SAF2016-76004-Rinfo:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/PID2019-105344RB-I00PID2019-105344RB-I00/AEI/10.13039/501100011033https://doi.org/10.3390/ijms22031161Síinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/2279552026-05-22T06:33:51Z
dc.title.none.fl_str_mv Cardiomyocytes Derived from Induced Pluripotent Stem Cells as a Disease Model for Propionic Acidemia
title Cardiomyocytes Derived from Induced Pluripotent Stem Cells as a Disease Model for Propionic Acidemia
spellingShingle Cardiomyocytes Derived from Induced Pluripotent Stem Cells as a Disease Model for Propionic Acidemia
Alonso-Barroso, Esmeralda
Propionic acidemia
Cardiac dysfunction
iPSC
iPSC-derived cardiomyocytes
Disease model
title_short Cardiomyocytes Derived from Induced Pluripotent Stem Cells as a Disease Model for Propionic Acidemia
title_full Cardiomyocytes Derived from Induced Pluripotent Stem Cells as a Disease Model for Propionic Acidemia
title_fullStr Cardiomyocytes Derived from Induced Pluripotent Stem Cells as a Disease Model for Propionic Acidemia
title_full_unstemmed Cardiomyocytes Derived from Induced Pluripotent Stem Cells as a Disease Model for Propionic Acidemia
title_sort Cardiomyocytes Derived from Induced Pluripotent Stem Cells as a Disease Model for Propionic Acidemia
dc.creator.none.fl_str_mv Alonso-Barroso, Esmeralda
Pérez, Belén
Ruiz Desviat, Lourdes
Richard, Eva
author Alonso-Barroso, Esmeralda
author_facet Alonso-Barroso, Esmeralda
Pérez, Belén
Ruiz Desviat, Lourdes
Richard, Eva
author_role author
author2 Pérez, Belén
Ruiz Desviat, Lourdes
Richard, Eva
author2_role author
author
author
dc.contributor.none.fl_str_mv Ministerio de Ciencia, Innovación y Universidades (España)
Agencia Estatal de Investigación (España)
Fundación Isabel Gemio
La Caixa
Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]
dc.subject.none.fl_str_mv Propionic acidemia
Cardiac dysfunction
iPSC
iPSC-derived cardiomyocytes
Disease model
topic Propionic acidemia
Cardiac dysfunction
iPSC
iPSC-derived cardiomyocytes
Disease model
description © 2021 by the authors
publishDate 2021
dc.date.none.fl_str_mv 2021
2021
2021
2021
dc.type.none.fl_str_mv info:eu-repo/semantics/article
http://purl.org/coar/resource_type/c_6501
Publisher's version
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10261/227955
url http://hdl.handle.net/10261/227955
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
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info:eu-repo/grantAgreement/MINECO/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016/SAF2016-76004-R
info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/PID2019-105344RB-I00
PID2019-105344RB-I00/AEI/10.13039/501100011033
https://doi.org/10.3390/ijms22031161
Sí
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv Multidisciplinary Digital Publishing Institute
publisher.none.fl_str_mv Multidisciplinary Digital Publishing Institute
dc.source.none.fl_str_mv reponame:DIGITAL.CSIC. Repositorio Institucional del CSIC
instname:Consejo Superior de Investigaciones Científicas (CSIC)
instname_str Consejo Superior de Investigaciones Científicas (CSIC)
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collection DIGITAL.CSIC. Repositorio Institucional del CSIC
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