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Generation of a High Number of Healthy Erythroid Cells from Gene-Edited Pyruvate Kinase Deficiency Patient-Specific Induced Pluripotent Stem Cells

2015-12-08Journal article Open access
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dc.contributor.authorGarate, Z
dc.contributor.authorQuintana-Bustamante, O
dc.contributor.authorCrane, AM
dc.contributor.authorOlivier, E
dc.contributor.authorPoirot, L
dc.contributor.authorGaletto, R
dc.contributor.authorKosinski, P
dc.contributor.authorHill, C
dc.contributor.authorKung, C
dc.contributor.authorAgirre, X
dc.contributor.authorOrman, I
dc.contributor.authorCerrato, L
dc.contributor.authorAlberquilla, O
dc.contributor.authorRodriguez-Fornes, F
dc.contributor.authorFusaki, N
dc.contributor.authorGarcia-Sanchez, F
dc.contributor.authorMaia, TM
dc.contributor.authorRibeiro, ML
dc.contributor.authorSevilla, J
dc.contributor.authorProsper, F
dc.contributor.authorJin, S
dc.contributor.authorMountford, J
dc.contributor.authorGuenechea, G
dc.contributor.authorGouble, A
dc.contributor.authorBueren, JA
dc.contributor.authorDavis, BR
dc.contributor.authorSegovia, JC
dc.date.accessioned2017-08-29T15:21:32Z
dc.date.available2017-08-29T15:21:32Z
dc.date.issued2015-12-08
dc.description.abstractPyruvate kinase deficiency (PKD) is a rare erythroid metabolic disease caused by mutations in the PKLR gene. Erythrocytes from PKD patients show an energetic imbalance causing chronic non-spherocytic hemolytic anemia, as pyruvate kinase defects impair ATP production in erythrocytes. We generated PKD induced pluripotent stem cells (PKDiPSCs) from peripheral blood mononuclear cells (PB-MNCs) of PKD patients by non-integrative Sendai viral vectors. PKDiPSCs were gene edited to integrate a partial codon-optimized R-type pyruvate kinase cDNA in the second intron of the PKLR gene by TALEN-mediated homologous recombination (HR). Notably, we found allele specificity of HR led by the presence of a single-nucleotide polymorphism. High numbers of erythroid cells derived from gene-edited PKDiPSCs showed correction of the energetic imbalance, providing an approach to correct metabolic erythroid diseases and demonstrating the practicality of this approach to generate the large cell numbers required for comprehensive biochemical and metabolic erythroid analyses.pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationStem Cell Reports. 2015 Dec 8;5(6):1053-66.pt_PT
dc.identifier.doi10.1016/j.stemcr.2015.10.002pt_PT
dc.identifier.urihttp://hdl.handle.net/10400.4/2083
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.subjectAnemia Hemolítica Congénita não Esferocíticapt_PT
dc.subjectCélulas Eritroidespt_PT
dc.subjectCélulas-Tronco Pluripotentes Induzidaspt_PT
dc.subjectPiruvato Quinasept_PT
dc.subjectErros Inatos do Metabolismo dos Piruvatospt_PT
dc.titleGeneration of a High Number of Healthy Erythroid Cells from Gene-Edited Pyruvate Kinase Deficiency Patient-Specific Induced Pluripotent Stem Cellspt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.citation.endPage1066pt_PT
oaire.citation.issue6pt_PT
oaire.citation.startPage1053-66pt_PT
oaire.citation.volume5pt_PT
rcaap.rightsopenAccesspt_PT
rcaap.typearticlept_PT

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