SNP analysis of human induced pluripotent stem cells
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE31035 | GEO | 2011/09/01
SECONDARY ACCESSION(S): PRJNA144907
REPOSITORIES: GEO
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Project description:Human induced pluripotent stem cells (hIPSCs) represent a unique opportunity for regenerative medicine since they offer the prospect of generating unlimited quantities of cells for autologous transplantation as a novel treatment for a broad range of disorders. However, the use of hIPSCs in the context of genetically inherited human disease will require correction of disease-causing mutations in a manner that is fully compatible with clinical applications. Genomic instability induced by reprogramming or genetic modification would be a main issue for the safe use of these cells. We analyzed primary hIPSC lines and genetically modified derivatives by array-based comparative genomic hybridization.
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Project description:Human induced pluripotent stem cells (hIPSCs) represent a unique opportunity for regenerative medicine since they offer the prospect of generating unlimited quantities of cells for autologous transplantation as a novel treatment for a broad range of disorders. However, the use of hIPSCs in the context of genetically inherited human disease will require correction of disease-causing mutations in a manner that is fully compatible with clinical applications. We analyzed hiPSC line and genetically modified derivatives using high-density SNP array to investigate genomic instability associated reprogramming and genetic modification. Primary iPSC lines derived from patients with alpha-1 antitrypsin deficiency were generated. This genetic disorder is caused by homozygous mutation (Glu342Lys) in the SERPINA1 gene. We carried out mutation correction by 2 steps: zinc-finger nuclease-stimuated gene targeting and piggyBac trasnsposon-mediated selection cassette elimination. Parental fibroblast lines, primary iPSC lines and homozygously targeted iPSC lines were subjected to SNP genotyping using Illumina CytoSNP-12 BeadChiP.
2011-08-31 | E-GEOD-31035 | biostudies-arrayexpress
Project description:Human induced pluripotent stem cells (hIPSCs) represent a unique opportunity for regenerative medicine since they offer the prospect of generating unlimited quantities of cells for autologous transplantation as a novel treatment for a broad range of disorders. It is now known that primary iPS cells often carry genomic aberrations and these abnormality may compromise their possibility of clinical application. We analysed primary hIPSC lines derived from monoclonal human endothelial progenitor cell lines by array-based comparative genomic hybridisation.
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Project description:Human induced pluripotent stem cells (hiPSCs) have potential for personalized and regenerative medicine. While most methods of utilizing these cells have focused on deriving homogenous populations of specialized cells, there has been modest success in producing hiPSC-derived organotypic tissues or organoids. Here we present a novel approach for generating and then co-differentiating hiPSC-derived progenitors. With a genetically engineered pulse of GATA6 expression, we initiate rapid emergence of all three germ layers as a complex function of GATA6 expression levels and tissue context. Within two weeks we obtain a complex tissue that recapitulates early developmental processes and exhibits a liver bud-like phenotype, including haematopoietic and stromal cells, as well as a neuronal niche. Our approach addresses two major issues in derivation of tissues from hiPSCs: using a single autologous hiPSCs as source and generating a range of stromal cells that co-develop with parenchymal cells to form complex tissues. Gene expression profiling (microarray) of iPS cells (PGP1) at X days post- doxycycline induction of mouse Gata6. Either total cells or immunomagnetic isolation of cells with specific surface markers. Three samples per group.
2015-11-05 | E-GEOD-74662 | biostudies-arrayexpress
Project description:Human induced pluripotent stem cells (hiPSCs) have potential for personalized and regenerative medicine. While most methods of utilizing these cells have focused on deriving homogenous populations of specialized cells, there has been modest success in producing hiPSC-derived organotypic tissues or organoids. Here we present a novel approach for generating and then co-differentiating hiPSC-derived progenitors. With a genetically engineered pulse of GATA6 expression, we initiate rapid emergence of all three germ layers as a complex function of GATA6 expression levels and tissue context. Within two weeks we obtain a complex tissue that recapitulates early developmental processes and exhibits a liver bud-like phenotype, including haematopoietic and stromal cells, as well as a neuronal niche. Our approach addresses two major issues in derivation of tissues from hiPSCs: using a single autologous hiPSCs as source and generating a range of stromal cells that co-develop with parenchymal cells to form complex tissues.
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Project description:Patient-specific induced pluripotent stem cells (iPSCs) derived from somatic cells provide a unique tool for the study of human disease in disease relevant cells, as well as a promising source for cell replacement therapies for degenerative diseases. However one of the crucial limitations before realizing the full promise of this “disease in a dish” approach has been the inability to do controlled experiments under genetically defined conditions. This is particularly relevant for disorders with long latency periods, such as Parkinson’s disease (PD), where in vitro phenotypes of patient-derived iPSCs are predicted to be subtle and susceptible to significant epistatic effects of genetic background variations. By combining zinc-finger nuclease (ZFN)-mediated genome editing and iPSC technology we provide a generally applicable solution to this key problem by generating isogenic pairs of disease and control human embryonic stem cells (hESCs) and hiPSCs lines that differ exclusively at a susceptibility variant for PD by modifying a single point mutation (A53T) in the α-synuclein gene. The robust capability to genetically correct disease causing point mutations in patient-derived hiPSCs represents not only a significant progress for basic biomedical research but also a major advancement towards hiPSC-based cell replacement therapies using autologous cells. ZFN-mediated genome edited human iPS cells or ES cells were assayed for gene expression
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Project description:Patient-specific induced pluripotent stem cells (iPSCs) derived from somatic cells provide a unique tool for the study of human disease in disease relevant cells, as well as a promising source for cell replacement therapies for degenerative diseases. However one of the crucial limitations before realizing the full promise of this “disease in a dish” approach has been the inability to do controlled experiments under genetically defined conditions. This is particularly relevant for disorders with long latency periods, such as Parkinson’s disease (PD), where in vitro phenotypes of patient-derived iPSCs are predicted to be subtle and susceptible to significant epistatic effects of genetic background variations. By combining zinc-finger nuclease (ZFN)-mediated genome editing and iPSC technology we provide a generally applicable solution to this key problem by generating isogenic pairs of disease and control human embryonic stem cells (hESCs) and hiPSCs lines that differ exclusively at a susceptibility variant for PD by modifying a single point mutation (A53T) in the ?-synuclein gene. The robust capability to genetically correct disease causing point mutations in patient-derived hiPSCs represents not only a significant progress for basic biomedical research but also a major advancement towards hiPSC-based cell replacement therapies using autologous cells. ZFN-mediated genome edited human iPS cells or ES cells were assayed for genomic variation
2011-07-25 | E-GEOD-29772 | biostudies-arrayexpress
Project description:Cornelia de Lange syndrome (CdLS) is an autosomal dominant disease mainly caused by mutations in the Nipped-B-like protein (NIPBL) gene resulting in the alteration of the cohesin pathway. Here, we generated human induced pluripotent stem cells (hiPSCs) from a CdLS patient carrying a mutation in the NIPBL gene, c.5483G>A, and tested CRISPR-Cas based approaches to repair the genetic defect. We applied an efficient and precise method of gene correction through CRISPR-Cas induced homology directed repair (HDR), which allowed the generation of hiPSC clones with regular karyotype and preserved stemness. The efficient and precise gene replacement strategy developed in this study can be extended to the modification of other genomic loci in hiPSCs. Isogenic wild-type and mutated hiPSCs produced with the CRISPR-Cas technology are fundamental CdLS cellular models to study the disease molecular determinants and identifying therapeutic targets.
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