Genome-wide expression profiling and functional characterization of SCA28 lymphoblastoid cell lines.
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE42406 | GEO | 2013/06/21
SECONDARY ACCESSION(S): PRJNA181309
REPOSITORIES: GEO
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Project description:To identify altered pathways in SCA28 LCLs, we performed a whole genome expression profiling, based on Affymetrix Human Genome U133A 2.0 Chip Array, on LCLs from four unrelated patients, each carrying a different AFG3L2 mutation. Gene expression profiling of 4 patients and 6 healthy controls
2013-06-21 | E-GEOD-42406 | biostudies-arrayexpress
Project description:We hypothesized that mapping genetic variants associated with promoter and enhancer functions can provide novel insights into the mechanism through which eQTLs (expression quantitative trait loci) exert their effects on gene expression. To this end, we quantified genome-wide promoter usage and enhancer activity and tested the resulting molecular phenotypes for association with nearby genetic variants to discover cis-QTLs. To perform such analyzes, we have produced deep transcriptome profiling of 154 unrelated central European individuals, applying deepCAGE (Cap Analysis of Gene Expression) to nuclear enriched total RNA extracted from EBV transformed lymphoblastoid cell lines (LCLs). The LCLs were either purchased from Coriell Cell Repository (CEU, n=86) or from the GenCord collection (n=68, Gutierrez-Arcelus M et al. Elife 2013).
2017-09-15 | E-MTAB-5835 | biostudies-arrayexpress
Project description:We used microarrays to identify the variation of basal gene expression level among 287 lymphoblastoid cell lines. Radiation therapy is used to treat half of all cancer patients. Response to radiation therapy varies widely among patients. Therefore, we performed a genome-wide association study (GWAS) to identify biomarkers to help predict radiation response using 277 ethnically defined human lymphoblastoid cell lines (LCLs). Basal gene expression levels and 1.3 million genome-wide SNP markers from both Affymetrix and Illumina platforms were assayed for all 277 human LCLs. MTS (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium) assays for radiation cytotoxicity were also performed to obtain area under the curve (AUC) as a radiation response phenotype for use in the association studies. Functional validation of candidate genes, selected from an integrated analysis that used SNP, expression and AUC data, was performed with multiple cancer cell lines using specific siRNA knockdown, followed by MTS and colony-forming assays. 27 loci, each containing at least 2 SNPs within 50kb with p-values <10-4, were associated with radiation AUC. 270 expression probe sets were associated with radiation AUC with p<10-3. The integrated analysis identified 50 SNPs in 14 of the 27 loci that were associated with both AUC and the expression of 39 genes that were also associated with radiation AUC (p<10-3). Functional validation using siRNA knockdown in multiple tumor cell lines showed that C13orf34, MAD2L1, PLK4, TPD52 and DEPDC1B each significantly altered radiation sensitivity in at least 2 cancer cell lines. Studies performed with LCLs can help to identify novel biomarkers that might contribute to variation in response to radiation therapy and enhance our understanding of mechanisms underlying that variation. EBV-transformed LCLs from 95 African-American (AA), 96 Caucasian-American (CA), and 96 Han Chinese-American (HCA) unrelated healthy subjects (sample sets HD100AA, HD100CAU, HD100CHI) were purchased from the Coriell Cell Repository (Camden, NJ).
2010-07-24 | E-GEOD-23120 | biostudies-arrayexpress
Project description:Epstein-Barr virus (EBV) transformed lymphoblastoid cell lines (LCLs) are a widely used renewable resource for functional genomic studies in humans. The ability to accumulate multidimensional data pertaining to the same individual cell lines, from complete genomic sequences to detailed gene regulatory profiles, further enhances the utility of LCLs as a model system. However, the extent to which LCLs are a faithful model system is relatively unknown. We have previously shown that gene expression profiles of newly established LCLs maintain a strong individual component. Here, we extend our study to investigate the effect of freeze-thaw cycles on gene expression patterns in mature LCLs, especially in the context of inter-individual variation in gene regulation. We found a profound difference in the gene expression profiles of newly established and mature LCLs. Once newly established LCLs undergo a freeze-thaw cycle, the individual specific gene expression signatures become much less pronounced as the gene regulatory programs in LCLs from different individuals converge to a more uniform profile, which reflects a mature transformed B cell phenotype. As expected, previously identified eQTLs are enriched among the relatively few genes whose regulations in mature LCLs maintain marked individual signatures. We thus conclude that findings and insight drawn from gene regulatory studies in mature LCLs are generally not affected by artificial nature of the LCL model system and are likely to faithfully reflect regulatory interactions in primary tissues. However, our data indicate that many aspects of primary B cell biology cannot be observed and studied in mature LCL cultures. We obtained unpurified buffy coats (of a unit of blood) from six unrelated healthy individuals of Caucasian ethnicity (age range: 20-45). We isolated CD20+ B cells and established six independent cultures of LCLs between October 2009 and January 2010. From each of these samples, we obtained genome wide gene expression data using Illumina HumanHT-12 v3 Expression BeadChip arrays. We refer to data from these experiments as M-bM-^@M-^\cycle 0M-bM-^@M-^] to acknowledge the fact that the LCLs from this cycle were newly established and therefore not frozen/thawed. Between February 2011 and October 2012, we thawed each of these LCL cultures every 3 months and cultured them until obtaining ~10 million cells (February 2011=cycle 1, June 2011=cycle 2, October 2011=cycle 3, February 2012=cycle 4, June 2012=cycle 5, and October 2012=cycle 6). We used Illumina HumanHT-12 v4 Expression BeadChip arrays and obtained genome wide gene expression data on cycle 2, cycle 4 and cycle 6 LCLs. At each hybridization batch we included a subset of RNA samples that were also hybridized in a previous batch. This allowed us to effectively consider the batch effect on gene expression profiles. Our final dataset included genome wide gene expression data from 187 samples collected at 4 different time points.
2014-09-05 | E-GEOD-58942 | biostudies-arrayexpress
Project description:Amyotrophic lateral sclerosis (ALS) consists in the progressive degeneration of motor neurons, caused by mechanisms that are poorly understood and for which there is no cure. Some of the cellular perturbations associated with ALS can be detected in peripheral cells, including lym-phocytes from blood. A related cell system that is very suitable for research consists in human lymphoblastoid cell lines (LCLs), which are immortalized lymphocytes. LCLs that can be easily expanded in culture and can be maintained for long periods of time as stable cultures. We inves-tigated, on a small set of LCLs, if proteomics analysis by liquid chromatography followed by tandem mass spectrometry reveals proteins that are differentially present in ALS versus healthy controls. We found that individual proteins and cellular and molecular pathways in which these proteins participate, are detected as differentially present in the ALS samples. Some of these proteins and pathways are already known to be perturbed in ALS, while others are new and present interest for further investigations. These observations suggest that more detailed pro-teomics analysis of LCLs, using a larger number of samples, represents a promising approach for investigating ALS mechanisms and to search for therapeutic agents.
2023-03-12 | PXD040240 | Pride
Project description:We report single-cell RNA sequencing datasets for three lymphoblastoid cell lines (LCLs) prepared by infection of primary B cells with Epstein-Barr Virus (EBV). Inter- and intra-sample transcriptional variance is observed with respect to immunoglobulin heavy chain class; host gene sets involved in survival, proliferation and differentiation; and viral replication state. We propose that the observed heterogeneity arises from the dynamic nature of host-pathogen interactions, donor-specific compositions of primary B cells, and other experimental factors such as stochastic clonal evolution in cell culture conditions.
2021-02-15 | GSE158275 | GEO
Project description:Epstein-Barr virus (EBV) transformed lymphoblastoid cell lines (LCLs) are a widely used renewable resource for functional genomic studies in humans. The ability to accumulate multidimensional data pertaining to the same individual cell lines, from complete genomic sequences to detailed gene regulatory profiles, further enhances the utility of LCLs as a model system. However, the extent to which LCLs are a faithful model system is relatively unknown. We have previously shown that gene expression profiles of newly established LCLs maintain a strong individual component. Here, we extend our study to investigate the effect of freeze-thaw cycles on gene expression patterns in mature LCLs, especially in the context of inter-individual variation in gene regulation. We found a profound difference in the gene expression profiles of newly established and mature LCLs. Once newly established LCLs undergo a freeze-thaw cycle, the individual specific gene expression signatures become much less pronounced as the gene regulatory programs in LCLs from different individuals converge to a more uniform profile, which reflects a mature transformed B cell phenotype. As expected, previously identified eQTLs are enriched among the relatively few genes whose regulations in mature LCLs maintain marked individual signatures. We thus conclude that findings and insight drawn from gene regulatory studies in mature LCLs are generally not affected by artificial nature of the LCL model system and are likely to faithfully reflect regulatory interactions in primary tissues. However, our data indicate that many aspects of primary B cell biology cannot be observed and studied in mature LCL cultures.
2014-09-05 | GSE58942 | GEO
Project description:Genome wide DNA methylation profiling of control and neurodevelopmental disorder lymphoblastoid cell lines (LCL). The Illumina Infinium 27k Human DNA methylation Beadchip v1.2 was used to obtain DNA methylation profiles across approximately 27,000 CpGs in LCLs. Samples included 19 control, 18 Rett syndrome, 17 autism and 6 generalized epilepsy LCL samples. Six technical replicates were also included in the analysis.
2012-12-01 | GSE34099 | GEO
Project description:Epstein Barr virus (EBV) nuclear antigen 3C (EBNA3C) is an essential transcription factor for initiating and maintaining human B lymphocyte transformation to lymphoblastoid cell lines (LCLs). To comprehensively identify EBNA3C regulated cell genes in LCLs, oligonucleotide arrays were used to compare RNA abundances in 3 different LCLs transformed by an EBV that conditionally expresses EBNA3C. Cell RNA levels were assessed in actively growing LCLs, under non-permissive or permissive conditions or under non-permissive conditions after transcomplementation with wild type EBNA3C. A two-way ANOVA model with covariates including the 3 different clone effects and the 3 EBNA3C expression levels, identified 550 EBNA3C regulated genes, with False Discovery Rate <0.01 and >1.5 fold change. A seeded Bayesian network analysis of the 80 most significantly EBNA3C regulated genes that changed >1.5 fold, positioned RAC1, LYN and TNF upstream of other EBNA3C regulated genes. Further, Gene Set Enrichment Assay (GSEA) identified EBNA3C regulated genes to be enriched for MAP kinase signaling, cytokine-cytokine receptor interactions, JAK-STAT signaling, and cell adhesion molecule effects, implicating these pathways in LCL growth or survival. Moreover, 106 EBNA3C regulated genes could be placed in protein interaction networks. Since CXCL12 and CXCR4 signaling are implicated in LCL growth and were EBNA3C up-regulated, up-regulation of CXCL12 was validated by qRT-PCR and effects on induced LCL migration were confirmed. EBNA3C regulated genes significantly overlapped with EBNA2 and EBNA3A regulated genes, consistent with a central role for RBP/CSL in these effects. RNAs from three different Lymphoblastoid Cell Lines(LCLs) expressing conditional EBNA3C grown under permissive or non-permissive conditions for 7 days; the same LCLs transcompletemented with EBNA3C expressed in trans at full wild-type level were used to identify EBNA3C regualted cellular genes. Total cell RNAs were hybrdized to Affymetrix U-133 Plus 2.0 microarrays. A two way ANOVA model was developed with covariates including the 3 different clone effects and the 3 EBNA3C expression levels and identified 550 EBNA3C regulated genes.
2011-01-06 | E-GEOD-24362 | biostudies-arrayexpress
Project description:Expression data from human lymphoblastoid cell lines (LCLs)
| PRJNA793048 | ENA