Filters
Technology
Platform
GSE60760
Homo sapiens
8 Downloadable Samples
Affymetrix Human Transcriptome Array 2.0 (hta20)
Description
Arsenic (As) exposure is a significant worldwide environmental health concern. Low dose, chronic arsenic exposure has been associated with higher risk of skin, lung, and bladder cancer, as well as cardiovascular disease and diabetes. While arsenic-induced biological changes play a role in disease pathology, little is known about the dynamic cellular changes due to arsenic exposure and withdrawal. In these studies, we seek to understand the molecular mechanisms behind the biological changes induced by chronic low doses of arsenic exposure. We used a comprehensive approach involving chromatin structural studies and mRNA microarray analyses to determine how chromatin structure and gene expression patterns change in response to chronic low dose arsenic exposure and its subsequent withdrawal. Our results show that cells exposed to low doses of sodium arsenite have distinct temporal and coordinated chromatin, gene expression and miRNA changes that are consistent with differentiation and activation of multiple biochemical pathways. Most of these temporal patterns in gene expression are reversed when arsenic was withdrawn. However, some of the gene expression patterns remained altered, plausibly as a result of an adaptive response by these cells. Additionally, these gene expression patterns correlated with changes in chromatin structure, further solidifying the role of chromatin structure in gene regulatory changes due to arsenite exposure. Lastly, we show that arsenite exposure influences gene regulation both at the transcription initiation as well as at the splicing level. Thus our results suggest that general patterns of alternative splicing, as well as expression of particular gene regulators, can be indicative of arsenite-induced cell transformation.
Publication Title
Inorganic Arsenic-induced cellular transformation is coupled with genome wide changes in chromatin structure, transcriptome and splicing patterns.
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 40 Downloadable Samples
- Affymetrix Human Exon 1.0 ST Array [probe set (exon) version (huex10st)
Description
Alternative processing of pre-mRNA transcripts is a major source of protein diversity in eukaryotes and has been implicated in several disease processes including cancer. In this study we have performed a genome wide analysis of alternative splicing events with the GeneChip Human Exon 1.0 ST Array from Affymetrix in lung adenocarcinoma. We found that ~13.3% of the 17800 core Refseq genes appear to have alternative transcripts that are differentially expressed in lung adenocarcinoma versus normal. According to their known functions the largest subset of these genes (30.8%) is believed to be cancer related. Detailed analysis was performed for several genes using PCR, quantitative RT-PCR and DNA sequencing. We found overexpression of ERG variant 2 but not variant 1 in lung tumors and overexpression of CEACAM1 variant 1 but not variant 2 in lung tumors but not in breast or colon tumors. We also identified a novel, overexpressed variant of CDH3 and verified the overexpression of a novel variant of P16. These findings demonstrate how analysis of alternative pre-mRNA processing can shed additional light on differences between tumors and normal tissues as well as between different tumor types. Such studies may lead to the development of additional tools for tumor diagnosis, prognosis and therapy.
Publication Title
Whole genome exon arrays identify differential expression of alternatively spliced, cancer-related genes in lung cancer.
Sample Metadata Fields
Sex, Age, Race, Subject
View Samples- Mus musculus
- 6 Downloadable Samples
NextSeq 500
Description
Bone mineral density (BMD) is a strong predictor of osteoporotic fracture. It is also one of the most heritable disease-associated quantitative traits. As a result, there has been considerable effort focused on dissecting its genetic basis. Here, we performed a genome-wide association study (GWAS) in a panel of inbred strains to identify associations influencing BMD. This analysis identified a significant (P=3.1 x 10-12) BMD locus on Chromosome 3@52.5 Mbp that replicated in two seperate inbred strain panels and overlapped a BMD quantitative trait locus (QTL) previously identified in a F2 intercross. The association mapped to a 300 Kbp region containing four genes; Gm2447, Gm20750, Cog6, and Lhfp. Â Further analysis found that Lipoma HMGIC Fusion Partner (Lhfp) was highly expressed in bone and osteoblasts and its expression was regulated by local expression QTL (eQTL) in multiple tissues. A co-expression network analysis revealed that Lhfp was strongly connected to genes involved in osteoblast differentiation. To directly evaluate its role in bone, Lhfp deficient mice (Lhfp-/-) were created using CRISPR/Cas9. Consistent with genetic and network predictions, bone marrow stromal cells (BMSCs) from Lhfp-/- displayed increased osteogenic differentiation. Lfhp-/- mice also had elevated BMD due to increased cortical bone mass. In conclusion, we used GWAS and systems genetics in mice to identify Lhfp as a regulator of osteoblast activity and bone mass. Overall design: Bones and osteoblast-derived from bone marrow stromal cells were profiles using RNA-seq from CC0016/GeniUnc mice (N=3 biological replicates per sample type)
Publication Title
Mouse genome-wide association and systems genetics identifies Lhfp as a regulator of bone mass.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Rattus norvegicus
- 68 Downloadable Samples
- Illumina HiSeq 2500
Description
Previous study has shown that alpha1ACT is a transcription factor involved with regulating neuronal gene expression. We performed a time-series RNA-seq study using pc12 cell lines stably expressing pcDNA3-alpha1ACT at 4 time points (6hr, 24hr, 3day, and 10day) to explore the transcriptional profiles that capture transient and prolonged dynamic changes regulated by alpha1ACT during cell cycle and differentiation Overall design: PC12 cell lines expressing pcDNA3 (EV) and expressing pcDNA3-a1ACT at 4 different time points (6h, 24h, 3d, 10d) were analyzed by Agilent Bio-analyzer and submitted to university of Chicago Functional genomic facility for library preparation (TruSeq Stranded Total RNA Library Prep Kit with Ribo-Zero Gold, RS-122-2301) and sequencing on Illumina HiSeq2500 platform, with 3 biological replicates for each condition.
Publication Title
α1ACT Is Essential for Survival and Early Cerebellar Programming in a Critical Neonatal Window.
Sample Metadata Fields
Specimen part, Cell line, Subject, Time
View Samples- Mus musculus
- 22 Downloadable Samples
- Affymetrix Mouse Gene 1.1 ST Array (mogene11st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Multi-level omics analysis in a murine model of dystrophin loss and therapeutic restoration.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Mus musculus
- 11 Downloadable Samples
- Affymetrix Mouse Gene 1.1 ST Array (mogene11st)
Description
Duchenne muscular dystrophy (DMD) is a classical monogenic disorder, a model disease for genomic studies and a priority candidate for regenerative medicine and gene therapy. Although the genetic cause of DMD is well known, the molecular pathogenesis of disease and the response to therapy are incompletely understood. Here,we describe analyses of protein, mRNA and microRNA expression in the tibialis anterior of the mdx mouse model of DMD. Notably, 3272 proteins were quantifiable and 525 identified as differentially expressed in mdx muscle (P < 0.01). Therapeutic restoration of dystrophin by exon skipping induced widespread shifts in protein and mRNA expression towards wild-type expression levels, whereas the miRNome was largely unaffected. Comparison analyses between datasets showed that protein and mRNA ratios were only weakly correlated (r = 0.405), and identified a multitude of differentially affected cellular pathways, upstream regulators and predicted miRNAtarget interactions. This study provides fundamental new insights into gene expression and regulation in dystrophic muscle.
Publication Title
Multi-level omics analysis in a murine model of dystrophin loss and therapeutic restoration.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Arabidopsis thaliana
- 6 Downloadable Samples
- Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)
Description
Redox Responsive Transcription Factor1 (RRTF1) in Arabidopsis is rapidly and transiently upregulated by H202, as well as biotic and abiotic induced redox signals. Inactivation of RRTF1 restricts and overexpression promotes reactive oxygen species (ROS) accumulation in response to stress. Overexpressor (oe) lines are impaired in root and shoot development, light sensitive and susceptible to Alternaria brassicae infection. These symptoms are diminished by the beneficial root endophyte Piriformospora indica which reduces ROS accumulation locally in roots and systemically in shoots, and by antioxidants and ROS inhibitors which scavenge ROS. More than 850 stress-, redox-, ROS regulated-, ROS scavenging-, defense-, cell death- and senescence-related genes are regulated by RRTF1, ~ 30% of them have ROS related functions. Bioinformatic analyses and in vitro DNA binding assays demonstrate that RRTF1 binds to GCC-box and GCC-box like sequences in the promoter of RRTF1-responsive genes. Upregulation of RRTF1 by stress stimuli as well as H2O2 requires WRKY18/40/60. RRTF1 is co-regulated with the phylogenetically related RAP2.6, which contains GCC-box like sequene in its promoter, but RAP2.6 oe lines do not accumulate higher ROS levels. RRTF1 stimulates systemic ROS accumulation in distal non-stressed leaves. We conclude that the highly conserved RRTF1 rapidly, transiently and systemically induce ROS accumulation in response to ROS and ROS-producing abiotic and biotic stress signals. Necrotrophs stimulate RRTF1 expression, while symbiotic interactions of Arabidopsis with (hemi)-biotrophs and P. indica do not affect or repress RRTF1 expression.
Publication Title
High REDOX RESPONSIVE TRANSCRIPTION FACTOR1 Levels Result in Accumulation of Reactive Oxygen Species in Arabidopsis thaliana Shoots and Roots.
Sample Metadata Fields
Specimen part
View Samples- Arabidopsis thaliana
- 6 Downloadable Samples
- Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)
Description
Redox Responsive Transcription Factor1 (RRTF1) in Arabidopsis is rapidly and transiently upregulated by H202, as well as biotic and abiotic induced redox signals. Inactivation of RRTF1 restricts and overexpression promotes reactive oxygen species (ROS) accumulation in response to stress. Overexpressor (oe) lines are impaired in root and shoot development, light sensitive and susceptible to Alternaria brassicae infection. These symptoms are diminished by the beneficial root endophyte Piriformospora indica which reduces ROS accumulation locally in roots and systemically in shoots, and by antioxidants and ROS inhibitors which scavenge ROS. More than 850 stress-, redox-, ROS regulated-, ROS scavenging-, defense-, cell death- and senescence-related genes are regulated by RRTF1, ~ 30% of them have ROS related functions. Bioinformatic analyses and in vitro DNA binding assays demonstrate that RRTF1 binds to GCC-box and GCC-box like sequences in the promoter of RRTF1-responsive genes. Upregulation of RRTF1 by stress stimuli as well as H2O2 requires WRKY18/40/60. RRTF1 is co-regulated with the phylogenetically related RAP2.6, which contains GCC-box like sequene in its promoter, but RAP2.6 oe lines do not accumulate higher ROS levels. RRTF1 stimulates systemic ROS accumulation in distal non-stressed leaves. We conclude that the highly conserved RRTF1 rapidly, transiently and systemically induce ROS accumulation in response to ROS and ROS-producing abiotic and biotic stress signals. Necrotrophs stimulate RRTF1 expression, while symbiotic interactions of Arabidopsis with (hemi)-biotrophs and P. indica do not affect or repress RRTF1 expression.
Publication Title
High REDOX RESPONSIVE TRANSCRIPTION FACTOR1 Levels Result in Accumulation of Reactive Oxygen Species in Arabidopsis thaliana Shoots and Roots.
Sample Metadata Fields
Age, Specimen part
View Samples- Mus musculus
- 2 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Adipose tissue iNKT cells have different functions than iNKT cells in the blood and other organs.
Publication Title
Regulatory iNKT cells lack expression of the transcription factor PLZF and control the homeostasis of T(reg) cells and macrophages in adipose tissue.
Sample Metadata Fields
Age, Specimen part
View Samples- Mus musculus
- 32 Downloadable Samples
- Illumina HiSeq 2000
Description
Natural killer T (NKT) cells identified by CD1d-tetramer and TCRb were isolated from the thymi of wild type and Ezh2 knockout mice. The NKT cells were FACS sorted into different stages based on the surface expression of CD44 and NK1.1. Overall design: For both wildtype and knockout mice, RNA was extracted from two biological replicates of CD44+ NK1.1- cells, one replicate of CD44+ NK1.1+ cells and one replicate of CD44- NK1.1- cells. Each RNA sample was divided into four and sequenced on four lanes of an Illumina HiSeq sequencer.
Publication Title
A non-canonical function of Ezh2 preserves immune homeostasis.
Sample Metadata Fields
Specimen part, Subject
View Samples