Fabry disease is an X-linked inherited disease caused by a mutation in the galactosidase alpha (GLA) gene. Here, we generated a GLA knock-out cell line (GLA-KO hiPSCs) from normal human-induced pluripotent stem cells (hFSiPS1) using the CRISPR-Cas9 genome-editing tool. The GLA-KO hiPSCs maintained normal morphology, karyotypes, expression of stemness markers, and trilineage differentiation potential. Furthermore, the GLA-KO hiPSCs exhibited dissipation of GLA activity and abnormal Globotriaosylceramide (Gb3) accumulation. Our GLA-KO hiPSC line represents a valuable tool for studying the mechanisms involved in Fabry disease and the development of novel therapeutic alternatives to treat this rare condition.
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CRISPR/Cas9-mediated suppression of A4GALT rescues endothelial cell dysfunction in a fabry disease vasculopathy model derived from human induced pluripotent stem cells.
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October 2024
Transplantation Research Center, College of Medicine, The Catholic University of Korea, Seoul, South Korea; Division of Nephrology, Department of Internal Medicine, Seoul St. Mary's Hospital, The College of Medicine, The Catholic University of Korea, South Korea. Electronic address:
Background And Aims: The objective of this study was to investigate the efficacy of CRISPR/Cas9-mediated A4GALT suppression in rescuing endothelial dysfunction in Fabry disease (FD) endothelial cells (FD-ECs) derived from human induced pluripotent stem cells (hiPSCs).
Methods: We differentiated hiPSCs (WT (wild-type), WTC-11), GLA-mutant hiPSCs (GLA-KO, CMC-Fb-002), and CRISPR/Cas9-mediated A4GALT-KO hiPSCs (GLA/A4GALT-KO, Fb-002-A4GALT-KO) into ECs and compared FD phenotypes and endothelial dysfunction. We also analyzed the effect of A4GALT suppression on reactive oxygen species (ROS) formation and transcriptome profiles through RNA sequencing.
CRISPR/Cas9-mediated A4GALT suppression rescues Fabry disease phenotypes in a kidney organoid model.
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Transplantation Research Center, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea; Division of Nephrology, Department of Internal Medicine, Seoul St. Mary's Hospital, The College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea. Electronic address:
The objective of this study was to investigate whether CRISPR/Cas9-mediated suppression of A4GALT could rescue phenotype of Fabry disease nephropathy (FDN) using human induced pluripotent stem cells (hiPSCs) derived kidney organoid system. We generated FDN patient-derived hiPSC (CMC-Fb-002) and FD-specific hiPSCs (GLA-KO) by knock-out (KO) of GLA in wild-type (WT) hiPSCs using CRISPR/Cas9. We then performed A4GALT KO in both CMC-Fb-002 and GLA-KO to make Fb-002-A4GALT-KO and GLA/A4GALT-KO, respectively.
View Article and Find Full Text PDFGeneration of a GLA knock-out human-induced pluripotent stem cell line, KSBCi002-A-1, using CRISPR/Cas9.
Stem Cell Res
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Daegu-Gyeongbuk Medical Innovation Foundation (DGMIF), 88 Dongnae-ro, Dong-gu, Daegu, Republic of Korea. Electronic address:
Fabry disease is an X-linked inherited disease caused by a mutation in the galactosidase alpha (GLA) gene. Here, we generated a GLA knock-out cell line (GLA-KO hiPSCs) from normal human-induced pluripotent stem cells (hFSiPS1) using the CRISPR-Cas9 genome-editing tool. The GLA-KO hiPSCs maintained normal morphology, karyotypes, expression of stemness markers, and trilineage differentiation potential.
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