Telomere Length Defines the Cardiomyocyte Differentiation Potency of Mouse Induced Pluripotent Stem Cells

dc.contributor.authorAguado Sánchez, Tania
dc.contributor.authorGutiérrez, Francisco J.
dc.contributor.authorAix, Esther
dc.contributor.authorSchneider, Ralph P.
dc.contributor.authorGiovinazzo, Giovanna
dc.contributor.authorBlasco, María A.
dc.contributor.authorFlores, Ignacio
dc.date.accessioned2023-12-19T15:51:47Z
dc.date.available2023-12-19T15:51:47Z
dc.date.issued2016-09-26
dc.description.abstractInduced pluripotent stem cells (iPSCs) can be differentiated in vitro and in vivo to all cardiovascular lineages and are therefore a promising cell source for cardiac regenerative therapy. However, iPSC lines do not all differentiate into cardiomyocytes (CMs) with the same efficiency. Here, we show that telomerase-competent iPSCs with relatively long telomeres and high expression of the shelterin-complex protein TRF1 (iPSChighT) differentiate sooner and more efficiently into CMs than those with relatively short telomeres and low TRF1 expression (iPSClowT). Ascorbic acid, an enhancer of cardiomyocyte differentiation, further increases the cardiomyocyte yield from iPSChighT but does not rescue the cardiomyogenic potential of iPSClowT. Interestingly, although iPSCslowT differentiate very poorly to the mesoderm and endoderm lineages, they differentiate very efficiently to the ectoderm lineage, indicating that cell fate can be determined by in vitro selection of iPSCs with different telomere content. Our findings highlight the importance of selecting iPSCs with ample telomere reserves in order to generate high numbers of CMs in a fast, reliable, and efficient way.
dc.description.departmentDepto. de Bioquímica y Biología Molecular
dc.description.facultyFac. de Ciencias Biológicas
dc.description.refereedTRUE
dc.description.sponsorshipMinisterio de Economía, Industria y Competitividad (MINECO)
dc.description.sponsorshipFundación Pro-CNIC
dc.description.sponsorshipCentro de Excelencia Severo Ochoa
dc.description.sponsorshipConsejo Europeo de Investigación (ERC)
dc.description.sponsorshipComunidad de Madrid
dc.description.sponsorshipFundación Botín
dc.description.sponsorshipFondo de Investigación AXA
dc.description.sponsorshipRed Temática de Investigación Cooperativa en Enfermedades Cardiovasculares
dc.description.sponsorshipMinisterio de Educación
dc.description.sponsorshipAsociación Española Contra el Cáncer (AECC)
dc.description.statuspub
dc.identifier.doi10.1002/stem.2497
dc.identifier.essn1549-4918
dc.identifier.issn1066-5099
dc.identifier.officialurlhttps://academic.oup.com/stmcls/article/35/2/362/6421128?login=true
dc.identifier.urihttps://hdl.handle.net/20.500.14352/91532
dc.issue.number2
dc.journal.titleStem Cells
dc.language.isoeng
dc.page.final373
dc.page.initial362
dc.publisherOxford University Press
dc.relation.projectID(SAF2013-45111RETOS), (SAF2012-38449)
dc.relation.projectID(SAF2013-45111RETOS)
dc.relation.projectID(GA#232854)
dc.relation.projectID(RD12/0042/0045)
dc.rights.accessRightsrestricted access
dc.subject.cdu602.9
dc.subject.keywordInduced pluripotent stem cells
dc.subject.keywordTelomere length
dc.subject.keywordCardiomyocytes
dc.subject.keywordExtracellular matrix
dc.subject.keywordAscorbic acid
dc.subject.ucmBiología celular (Biología)
dc.subject.ucmMedicina
dc.subject.unesco2407 Biología Celular
dc.subject.unesco32 Ciencias Médicas
dc.titleTelomere Length Defines the Cardiomyocyte Differentiation Potency of Mouse Induced Pluripotent Stem Cells
dc.typejournal article
dc.type.hasVersionVoR
dc.volume.number35
dspace.entity.typePublication
relation.isAuthorOfPublicationbde4a39d-9dc8-42b0-9f07-fb332f13c2d6
relation.isAuthorOfPublication.latestForDiscoverybde4a39d-9dc8-42b0-9f07-fb332f13c2d6
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