01e5da70-fec2-4218-bbbe-2e26efa666ba - samples
Ontology highlight
ABSTRACT:
PROVIDER: EGAD00001008094 | EGA |
REPOSITORIES: EGA
Similar Datasets
Project description:Nijmegen breakage syndrome (NBS) results from the absence of the NBS1 protein, responsible for detection of DNA double-strand breaks (DSBs). NBS is characterized by microcephaly, growth retardation, immunodeficiency, and cancer predisposition. Here we show successful reprogramming of NBS fibroblasts into induced pluripotent stem cells (NBS-iPSCs). Our data suggest a strong selection for karyotypically normal fibroblasts to go through the reprogramming process. NBS-iPSCs then acquire numerous chromosomal aberrations and show a delayed response to DSB induction. Furthermore, NBS-iPSCs display slower growth, mitotic inhibition, a reduced apoptotic response to stress and abnormal cell cycle-related gene expression. Importantly, NBS neural progenitor cells (NBS-NPCs) show down-regulation of neural developmental genes, which seems to be mediated by P53. Our results demonstrate the importance of NBS1 in early human development, shed new light on the molecular mechanisms underlying this severe syndrome and further expand our knowledge of the genomic stress cells experience during the reprogramming process. Gene expression analysis was performed on a total of 6 human cell lines, including WT and NBS Neural progenitor cells (NPCs) and NBS-iPSCs
2016-07-19 | E-GEOD-83686 | biostudies-arrayexpress
Project description:<p>Variability in induced pluripotent stem cell (iPSC) lines remains a roadblock for disease modeling and regenerative medicine. Through linear mixed models we have described different sources of gene expression variability from RNA sequencing data in 317 human iPSC lines from 101 individuals. We found that ~50% of genome-wide expression variability is explained by variation across individuals and identified a set of expression quantitative trait loci that contribute to this variation. These analyses coupled with allele specific expression show that iPSCs retain a subject-specific gene expression pattern. Pathway enrichment and key driver analyses, based on predictive causal gene networks, found that Polycomb targets explain a significant part of the non-genetic variability present in iPSCs within and across individuals. These publically available iPSC lines and genetic datasets will be a resource to the scientific community and will open new avenues to reduce variability in iPSCs and improve their utility in disease modeling.</p> <p>SNP array data from individuals included in RNA-seq transcriptome profiling study of human induced pluripotent stem cells to characterize gene expression variation across individuals and within multiple iPSC lines from the same individual. Genotyping was performed on patient blood.</p> Data availability: <ul> <li>SNP-genotyping: dbGaP - current study</li> <li>RNA-seq counts: <a href="http://www.ncbi.nlm.nih.gov/geo/">GEO</a> - GSE79636</li> <li>FASTQ files: <a href="http://www.ncbi.nlm.nih.gov/sra">SRA</a> - SRP072417</li> </ul>
| phs001139 | dbGaP
Project description:We generated induced pluripotent stem cell lines (iPSCs) from paired RTS patient/ parental control fibroblasts. These iPSCs were differentiated to mesenchymal stem cells (MSCs), and then to osteoblasts. We next compared the transcriptional profiles of MSCs, pre-osteoblasts, and osteoblasts.
2021-12-01 | GSE174720 | GEO
Project description:Pluripotent cells can be derived from somatic cells by either overexpression of defined transcription factors (resulting in induced pluripotent stem cells (iPSCs)) or by nuclear transfer or cloning (resulting in NT-ESCs). To determine whether cloning further reprograms iPSCs, we used iPSCs as donor cells in nuclear transfer experiments. An iPSC clone derived from tail-tip fibroblasts using adenoviral vectors was used as donor cell in nuclear transfer experiments. RNA was isolated from both parental iPSC clone and derivative NT-ESCs lines and analyzed.
2010-05-27 | E-GEOD-20575 | biostudies-arrayexpress
Project description:Trisomy of human chromosome 21 (T21) gives rise to Down syndrome, the most frequent life-born autosomal aneuploidy. To enable in vitro analyses of the cellular and moelcular mechanisms leading to the neurological alterations associated with T21, we created and characterized a panel of genomically diverse T21 and euploid induced pluripotent stem cells (iPSCs) from fibroblasts obtained from the Coriell Institute for Biomedical Research, and we then differentiated these iPSCs into neural progenitor cells (NPCs). Microarray transcriptomic analyses were performed on this panel of fibroblasts, iPSCs, and NPCs, identifying genes and pathways that were altered in T21 lines relative to euploid as well as genes and pathways in NPCs that showed inter-individual variability.
2024-11-06 | GSE273850 | GEO
Project description:Here, we determined the DNA methylation profiles of 12 human cell lines, including 2 ESC lines, 2 pESC lines,4 virally-delivered iPSC lines, 2 episomal-delivered iPSC lines, and 2 parent cell lines that iPSCs derived from using Illumina’s Infinium HumanMethylation450. The iPSCs exhibited a hypermethylation status similarly to ESCs but distinct differences from the parent cells. Genes of common methylation pattern between iPSCs and ESCs were regarded as critical factors for stemness, while differences existing between iPSCs and ESCs implied that iPSCs partly retained the parental characteristics and gained de novo methylation aberrances during cell reprogramming. No significant variant was identified between virally- and episomal- systems. De novo differentiated methylation regions as the signature of particular stem cell lines were figured out in detail in this study. 2 ESC lines, 2 pESC lines,4 virally-delivered iPSC lines, 2 episomal-delivered iPSC lines, and 2 parent cell lines that iPSCs derived from
2014-05-29 | E-GEOD-57992 | biostudies-arrayexpress
Project description:The differentiation capability of induced pluripotent stem cells (iPSCs) towards certain cell types for disease modelling and drug screening assays might be influenced by their somatic cell of origin. Here, we have compared the neural induction of human iPSCs generated from either fetal neural stem cells (fNSCs), dermal fibroblasts or CD34+ hematopoietic stem cells. Neural progenitor cells (NSCs) and neurons could be generated at similar efficiencies from all iPSCs. Whole genome transcriptome analysis and an expression analysis of neural genes in iPSC-derived NSCs revealed a separation of neuroectoderm- from mesoderm-derived cells. Furthermore, we found genes, which were similarly expressed between fNSCs and neuroectoderm- but not mesoderm-derived NSCs. Notably, these neural signatures were retained after transplantation into the cortex of mice and paralleled with increased survival and integration of neuroectoderm-derived cells in vivo. These results indicated distinct origin- dependent neural cell identities in differentiated human iPSCs both in vitro and in vivo.
2014-09-12 | GSE55107 | GEO
Project description:Induced pluripotent stem cells (iPSCs) are an essential tool for studying cellular differentiation and cell types that are otherwise difficult to access. We investigated the use of iPSCs and iPSC-derived cells to study the impact of genetic variation on gene regulation across different cell types and as models for studies of complex disease. To do so, we established a panel of iPSCs from 58 well-studied Yoruba lymphoblastoid cell lines (LCLs); 14 of these lines were further differentiated into cardiomyocytes. We characterized regulatory variation across individuals and cell types by measuring gene expression levels, chromatin accessibility and DNA methylation. Our analysis focused on a comparison of inter-individual regulatory variation across cell types. While most cell type-specific regulatory quantitative trait loci (QTLs) lie in chromatin that is open only in the affected cell types, we found that 20% of cell type-specific regulatory QTLs are in shared open chromatin. This observation motivated us to develop a deep neural network to predict open chromatin regions from DNA sequence alone. Using this approach, we were able to use the sequences of segregating haplotypes to predict the effects of common SNPs on cell type-specific chromatin accessibility.
2018-02-13 | GSE110544 | GEO
Project description:Induced pluripotent stem cells (iPSCs) are an essential tool for studying cellular differentiation and cell types that are otherwise difficult to access. We investigated the use of iPSCs and iPSC-derived cells to study the impact of genetic variation on gene regulation across different cell types and as models for studies of complex disease. To do so, we established a panel of iPSCs from 58 well-studied Yoruba lymphoblastoid cell lines (LCLs); 14 of these lines were further differentiated into cardiomyocytes. We characterized regulatory variation across individuals and cell types by measuring gene expression levels, chromatin accessibility and DNA methylation. Our analysis focused on a comparison of inter-individual regulatory variation across cell types. While most cell type-specific regulatory quantitative trait loci (QTLs) lie in chromatin that is open only in the affected cell types, we found that 20% of cell type-specific regulatory QTLs are in shared open chromatin. This observation motivated us to develop a deep neural network to predict open chromatin regions from DNA sequence alone. Using this approach, we were able to use the sequences of segregating haplotypes to predict the effects of common SNPs on cell type-specific chromatin accessibility.
2017-12-23 | GSE108460 | GEO
Project description:Induced pluripotent stem cells (iPSCs) are an essential tool for studying cellular differentiation and cell types that are otherwise difficult to access. We investigated the use of iPSCs and iPSC-derived cells to study the impact of genetic variation on gene regulation across different cell types and as models for studies of complex disease. To do so, we established a panel of iPSCs from 58 well-studied Yoruba lymphoblastoid cell lines (LCLs); 14 of these lines were further differentiated into cardiomyocytes. We characterized regulatory variation across individuals and cell types by measuring gene expression levels, chromatin accessibility and DNA methylation. Our analysis focused on a comparison of inter-individual regulatory variation across cell types. While most cell type-specific regulatory quantitative trait loci (QTLs) lie in chromatin that is open only in the affected cell types, we found that 20% of cell type-specific regulatory QTLs are in shared open chromatin. This observation motivated us to develop a deep neural network to predict open chromatin regions from DNA sequence alone. Using this approach, we were able to use the sequences of segregating haplotypes to predict the effects of common SNPs on cell type-specific chromatin accessibility.
2017-12-23 | GSE108459 | GEO