Please use this identifier to cite or link to this item: https://hdl.handle.net/20.500.12530/20155
Title: Generation of a High Number of Healthy Erythroid Cells from Gene-Edited Pyruvate Kinase Deficiency Patient-Specific Induced Pluripotent Stem Cells.
Authors: 
Mesh: 
Issue Date: 8-Dec-2015
Citation: Stem Cell Reports.2015 Dec;(5)6:1053-1066
Abstract: Pyruvate 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.
PMID: 26549847
URI: https://hdl.handle.net/20.500.12530/20155
Rights: openAccess
Appears in Collections:Fundaciones e Institutos de Investigación > FIB H. Infantil U. Niño Jesús > Artículos

Files in This Item:
File Description SizeFormat 
PMC4682065.pdf2.36 MBAdobe PDFThumbnail
View/Open


Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.