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GSE7955
Rattus norvegicus
60 Downloadable Samples
Affymetrix Rat Genome 230 2.0 Array (rat2302)
Description
Pyrethroids are neurotoxicants that disrupt nervous system function by interacting with a variety of membrane bound ion channels on neuronal plasma membranes. This study is designed to investigate the transcriptional events downstream of pyrethroid-induced disruption of nervous system excitability. Adult, male Long-Evans rats were orally dosed in vivo with a single dose of either permethrin (1, 10, or 100 mg/kg) or deltamethrin (0.3, 1, 3 mg/kg) at levels that produce only modest behaviroal effects in the whole animal (Wolansky et al. 2006). Transcriptional profiles were obtained from frontal cerebrocortical tissue 6 hours after acute exposure. The primary goals were 1) to identify dose-responsive biomarkers of effect for pyrethroids and 2) identify sensitive intracellular signaling or metabolic pathways sensitive to pyrethroid compounds.
Publication Title
Transcriptional response of rat frontal cortex following acute in vivo exposure to the pyrethroid insecticides permethrin and deltamethrin.
Sample Metadata Fields
Sex, Specimen part
View Samples- Homo sapiens
- 3 Downloadable Samples
IlluminaHiSeq2000
Description
Huntington’s disease (HD) is a devastating neurological disorder that is caused by an expansion of the poly-Q tract in exon 1 of the Huntingtin gene (HTT). HTT is an evolutionarily conserved and ubiquitously expressed protein that has been linked to a variety of functions including transcriptional regulation, mitochondrial function, and vesicle transport. This large protein has numerous caspase and calpain cleavage sites and can be decorated with several post-translational modifications such as phosphorylations, acetylations, sumoylations, and palmitoylations. However, the exact function of HTT and the role played by its modifications in the cell is still not well understood. Scrutiny of HTT function has been focused on a single, full length, mRNA. In this study, we report the discovery of 5 novel HTT mRNA splice isoforms that are expressed in normal and HD-hESC lines as well as cortical neurons differentiated from hESCs. Interestingly, none of the novel isoforms generates a truncated protein. Instead, 4 of the 5 new isoforms specifically eliminate domains and modifications to generate smaller HTT proteins. The fifth novel isoform incorporates a previously unreported additional exon, dubbed 41b, which is hominid-specific and introduces a potential phosphorylation site in the protein. The discovery of this hominid-specific isoform may shed light on human-specific pathogenic mechanisms of HTT, which could not be investigated with current mouse models of the disease. Furthermore, it provides a new human-specific target for drug screening in Huntington’s disease. Overall design: We performed RNAseq of human embryonic stem cells in pluripotency conditions to check expression of multiple HTT isoforms.
Publication Title
Discovery of novel isoforms of huntingtin reveals a new hominid-specific exon.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 22 Downloadable Samples
- Illumina HiSeq 2500
Description
Atopic dermatitis and psoriasis are driven by alternate type 2 and type 17 immune responses, but some proteins might be critical to both diseases. We show that a deficiency of the TNF superfamily molecule TWEAK (TNFSF12) in mice results in defective maintenance of atopic dermatitis-specific Th2 and psoriasis-specific Th17 cells in the skin, and impaired expression of disease-characteristic chemokines and cytokines, such as CCL17 and TSLP in atopic dermatitis, and CCL20 and IL-19 in psoriasis. The TWEAK receptor, Fn14, is upregulated in keratinocytes and dermal fibroblasts, and TWEAK induces these cytokines and chemokines alone and in synergy with the signature T helper cytokines of either disease, IL-13 and IL-17. Furthermore, subcutaneous injection of recombinant TWEAK into naïve mice induces cutaneous inflammation with histological and molecular signs of both diseases. TWEAK is therefore a critical contributor to skin inflammation and a possible therapeutic target in atopic dermatitis and psoriasis. Overall design: Eight- to 12-week old male mice were used. TWEAK-deficient animals were bred in house on the C57BL/6 background, and Fn14-deficient animals on a BALB/c. Atopic Dermatitis-like disease was induced by epicutaneous treatment with HDM extract (10 µg/mouse and treatment) and SEB (500 ng/mouse and treatment) given in 2 cycles on days 1 and 4, and 14 and 17, on the shaved and tape-stripped back skin over a 23 day period.
Publication Title
TWEAK mediates inflammation in experimental atopic dermatitis and psoriasis.
Sample Metadata Fields
Treatment, Subject
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Changes occur in the lung epithelium after allergen challenge that may give insight into asthma pathogenesis and we sought to identify novelepithelial genes induced by allergen exposure.
Publication Title
Alternaria induces STAT6-dependent acute airway eosinophilia and epithelial FIZZ1 expression that promotes airway fibrosis and epithelial thickness.
Sample Metadata Fields
Age, Specimen part
View Samples- Homo sapiens
- 3 Downloadable Samples
- Illumina HiSeq 2000
Description
Human pluripotent stem cells are a promising source of diverse cells for developmental studies, cell transplantation, disease modeling, and drug testing. However, their widespread use even for intensely studied cell types like spinal motor neurons, is hindered by the long duration and low yields of existing protocols for in vitro differentiation and by the molecular heterogeneity of the populations generated. We report a combination of small molecules that induce up to 50% motor neurons within 3 weeks from human pluripotent stem cells with defined subtype identities that are relevant to neurodegenerative diseases. Despite their accelerated differentiation, motor neurons expressed combinations of HB9, ISL1 and column-specific markers that mirror those observed in vivo in human fetal spinal cord. They also exhibited spontaneous and induced activity, and projected axons towards muscles when grafted into developing chick spinal cord. Strikingly, this novel protocol preferentially generates motor neurons expressing markers of limb-innervating lateral motor column motor neurons (FOXP1+/LHX3-). Access to high-yield cultures of human limb-innervating motor neuron subtypes will facilitate in-depth study of motor neuron subtype-specific properties, disease modeling, and development of large-scale cell-based screening assays. Overall design: We analyzed 3 samples including 2 positive samples and 1 negative sample. Descriptions are as follows: a) Positive Sample 1: SHH-derived, day 21 GFP-high FACS-purified motor neurons. b) Positive Sample 2: S+P-derived, day 21 GFP-high FACS-purified motor neurons. c) Negative: S+P condition, day 21 GFP-off FACS-purified non-motor neurons. Initial analysis of data was performed on ~40% of fastq reads (Amoroso et al., J Neurosci 2013 Jan 9;33(2):574-86. PMID: 23303937). Further processing of the full dataset has since been carried out and the updated rpkm file and expression analysis reflecting all aligned reads can be accessed at: http://scholar.harvard.edu/amorosornaseq/
Publication Title
Accelerated high-yield generation of limb-innervating motor neurons from human stem cells.
Sample Metadata Fields
Specimen part, Cell line, Treatment, Subject
View Samples- Homo sapiens
- 43 Downloadable Samples
- Affymetrix HT Human Genome U133A Array (hthgu133a)
Description
The developmental potential of human pluripotent stem cells suggests that they can produce disease-relevant cell types for biomedical research. However, substantial variation has been reported among pluripotent cell lines, which could affect their utility and clinical safety. Such cell-line specific differences must be better understood before one can confidently use embryonic stem (ES) or induced pluripotent stem (iPS) cells in translational research. Towards this goal we have established genome-wide reference maps of DNA methylation and gene expression for 20 previously derived human ES lines and 12 human iPS cell lines, and we have measured the in vitro differentiation propensity of these cell lines. This resource enabled us to assess the epigenetic and transcriptional similarity of ES and iPS cells and to predict the differentiation efficiency of individual cell lines. The combination of assays yields a scorecard for quick and comprehensive characterization of pluripotent cell lines.
Publication Title
Reference Maps of human ES and iPS cell variation enable high-throughput characterization of pluripotent cell lines.
Sample Metadata Fields
Sex, Cell line
View Samples- Homo sapiens
- 377 Downloadable Samples
- Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
Intensive lifestyle modification is believed to mediate cardiovascular disease (CVD) risk through traditional pathways that affect endothelial function and progression of atherosclerosis; however, the extent, persistence, and clinical significance of molecular change during lifestyle modification are not well known. Our study reveals that gene expression signatures are significantly modulated by rigorous lifestyle behaviors and track with CVD risk profiles over time.
Publication Title
Intensive cardiovascular risk reduction induces sustainable changes in expression of genes and pathways important to vascular function.
Sample Metadata Fields
Sex, Age
View Samples- Mus musculus
- 4 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
WNT5A inhibits metastasis and alters splicing of Cd44 in breast cancer cells.
Sample Metadata Fields
Cell line
View Samples- Mus musculus
- 4 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
A highly metastatic breast cancer cell line, 4T1, was used to generate stable Wnt5a expressing and vector only control cells. Cells were generated using lentivirus infection and selection with blasticidin. Expression of Wnt5a was confirmed using western blot. Cell behaviour was characterized. Wnt5a expressing cells exhibited reduced migration in a transwell assay and reduced metastasis in a tail vein injection assay. Growth was not significantly affected.
Publication Title
WNT5A inhibits metastasis and alters splicing of Cd44 in breast cancer cells.
Sample Metadata Fields
Cell line
View Samples- Mus musculus
- 4 Downloadable Samples
- NextSeq 500
Description
To investigate differential gene expression that might account for the differing glomerular phenotype of NPHS2-Cre +/+ mice when compared with wild-type control, including altered GBM thickness, loss of normal foot process morphology, and decrease in podocyte number, RNA sequencing analysis was performed on glomeruli extracted from both NPHS2-Cre +/+ and wild-type control mice. Overall design: Following isolation of glomeruli using Dynabeads from NPHS2-Cre +/+ and wild-type control mice (n=2 biological replicates per genotype, singly isolated), total RNA was extracted and RNA samples were submited for sample preparation and sequencing.
Publication Title
Podocyte-specific expression of Cre recombinase promotes glomerular basement membrane thickening.
Sample Metadata Fields
Sex, Age, Specimen part, Cell line, Subject
View Samples