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SRP078560
Homo sapiens
141 Downloadable Samples
Illumina HiSeq 2500
Description
Tuberculosis (TB) is responsible for the majority of mortality and morbidity associated with infectious diseases worldwide. The characterization of exact molecular components of immune response associated with protection against TB may help design more effective therapeutic interventions. In this study, we aimed to characterize the immune signature of memory T cells associated with latent infection with Mycobacterium tuberculosis. Transcriptomic profiling using RNA sequencing was performed on memory CD4 and CD8 T cells isolated from individuals with latent tuberculosis, as well as from tuberculosis negative healthy controls. Overall, we found specific gene signatures in each cell subset that could successfully discriminate between individuals with latent tuberculosis and healthy controls. Overall design: RNA-sequencing of sorted memory CD4 and CD8 T cells from cryopreserved PBMC of 10 subjects with latent tuberculosis infection and 10 tuberculosis negative healthy controls
Publication Title
Circulating T cell-monocyte complexes are markers of immune perturbations.
Sample Metadata Fields
Disease, Disease stage, Subject
View Samples- Homo sapiens
- 16 Downloadable Samples
Affymetrix Human Genome U133A Array (hgu133a)
Description
Rationale: Damage to airway epithelium is followed by deposition of extracellular matrix (ECM) and migration of adjacent epithelial cells. We have shown that epithelial cells from asthmatic children fail to heal a wound in vitro. Objectives: To determine whether dysregulated ECM production by the epithelium plays a role in aberrant repair in asthma. Methods: Airway epithelial cells (AEC) from children with asthma (n=36), healthy atopic (n=23) and healthy non-atopic controls (n=53) were investigated by microarray, gene expression and silencing, transcript regulation analysis and ability to close mechanical wounds. Results: Wound repair of AEC from healthy and atopic children were not significantly different and were both faster than AEC from asthmatics. Microarray analysis revealed differential expression of multiple gene sets associated with repair and remodeling in asthmatic AEC. Fibronectin (FN) was the only ECM component whose expression was significantly lower in asthmatic AEC. Expression differences were verified by qPCR and ELISA, and reduced FN expression persisted in asthmatic cells over passage. Silencing of FN expression in non-asthmatic AEC inhibited wound repair, while addition of FN to asthmatic AEC restored reparative capacity. Asthmatic AEC failed to synthesize FN in response to wounding or cytokine/growth factor stimulation. Exposure to 5, 2deoxyazacytidine had no effect on FN expression and subsequent analysis of the FN promoter did not show evidence of DNA methylation. Conclusions: These data show that the reduced capacity of asthmatic epithelial cells to secrete FN is an important contributor to the dysregulated AEC repair observed in these cells.
Publication Title
Decreased fibronectin production significantly contributes to dysregulated repair of asthmatic epithelium.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 11 Downloadable Samples
- Affymetrix Human Genome U95A Array (hgu95a)
Description
Gene expression profiling was performed on biopsies of affected and unaffected psoriatic skin and normal skin from seven Japanese patients to obtain insights into the pathways that control this disease. U95A Affymetrix DNA chips that contain oligonucleotide arrays of approximately 12,000 well-characterized human genes were used in the study. The statistical analysis of the Affymetrix data, based on the ranking of the Student-test statistic, revealed a complex regulation of molecular stress and immune gene responses. The majority of the 266 induced-genes in affected and unaffected psoriatic skin were involved with interferon mediation, immunity, cell-adhesion, cytoskeleton restructuring, protein trafficking and degradation, RNA regulation and degradation, signaling transduction, apoptosis and atypical epidermal cellular proliferation and differentiation. The disturbances in the normal protein degradation equilibrium of skin were reflected by the significant increase in the gene expression of various protease inhibitors and proteinases including the induced components of the ATP/ubiquitin-dependent non-lysosomal proteolytic pathway that is involved with peptide processing and presentation to T-cells. Some of the upregulated genes, such as TGM1, IVL, CSTA, FABP5 and SPRR, are well known psoriatic markers involved in atypical epidermal cellular organization and differentiation. In the comparison between the affected and unaffected psoriatic skin, the transcription factor JUNB was found at the top of the statistical rankings for the 51 significantly upregulated genes in affected skin, suggesting that it has an important but as yet undefined role in psoriasis. Our gene expression data and analysis suggest that psoriasis is a chronic IFN and T-cell-mediated immune disease of the skin where the imbalance in epidermal cellular structure, growth and differentiation arises from the molecular antiviral stress signals initiating inappropriate immune responses.
Publication Title
Gene expression profiling of Japanese psoriatic skin reveals an increased activity in molecular stress and immune response signals.
Sample Metadata Fields
No sample metadata fields
View Samples- Danio rerio
- 12 Downloadable Samples
- IlluminaHiSeq2000
Description
The basic helix-loop-helix factor Myod initiates skeletal muscle differentiation by directly and sequentially activating sets of muscle differentiation genes, including those encoding muscle contractile proteins. We hypothesize that Pbx homeodomain proteins direct Myod to a subset of its transcriptional targets, in particular fast twitch muscle differentiation genes, thereby regulating the competence of muscle precursor cells to differentiate. We have previously shown that Pbx proteins bind with Myod on the promoter of the zebrafish fast muscle gene mylpfa and that Pbx proteins are required for Myod to activate mylpfa expression and the fast-twitch muscle-specific differentiation program in zebrafish embryos. Here we have investigated the interactions of Pbx with another muscle fiber-type regulator, Prdm1a, a SET-domain DNA-binding factor that directly represses mylpfa expression and fast muscle differentiation. The prdm1a mutant phenotype, early and increased fast muscle differentiation, is the opposite of the Pbx-null phenotype, delayed and reduced fast muscle differentiation. To determine whether Pbx and Prdm1a have opposing activities on a common set of genes, we used RNA-seq analysis to globally assess gene expression in zebrafish embryos with single- and double-losses-of-function for Pbx and Prdm1a. We find that the levels of expression of certain fast muscle genes are increased or approximately wild type in pbx2/4-MO;prdm1a-/- embryos, suggesting that Pbx activity normally counters the repressive action of Prdm1a for a subset of the fast muscle program. However, other fast muscle genes require Pbx but are not regulated by Prdm1a. Thus, our findings reveal that subsets of the fast muscle program are differentially regulated by Pbx and Prdm1a. Our findings provide an example of how Pbx homeodomain proteins act in a balance with other transcription factors to regulate subsets of a cellular differentiation program. Overall design: Total RNA samples were genotyped and pooled for 4 sample types: control-MO;prdm1+/+; control-MO;prdm1-/-; pbx2/4-MO;prdm1+/+; and pbx2/4-MO;prdm1-/- embryos at the 10 somite (s) stage from three independent sets of egg collections/injections.
Publication Title
Pbx and Prdm1a transcription factors differentially regulate subsets of the fast skeletal muscle program in zebrafish.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 10 Downloadable Samples
- Illumina HiSeq 1500
Description
Facioscapulohumeral dystrophy (FSHD) is caused by the mis-expression of the double-homeodomain transcription factor DUX4 in skeletal muscle cells. Many different cell culture models have been developed to study the pathophysiology of FSHD, frequently based on endogenous expression of DUX4 in FSHD cells or by mis-expression of DUX4 in control human muscle cells. Although results generated using each model are generally consistent, differences have also been reported, making it unclear which model(s) faithfully recapitulate DUX4 and FSHD biology. In this study, we systematically compared RNA-seq data generated from three different models of FSHD—lentiviral-based DUX4 expression in myoblasts, doxycycline-inducible DUX4 in myoblasts, and differentiated human FSHD myocytes expressing endogenous DUX4—and show that the DUX4-associated gene expression signatures of each dataset are highly correlated (Pearson's correlation coefficient, r ~ 0.75-0.85). The few robust differences were attributable to different states of cell differentiation and other differences in experimental design. Our study describes a model system for inducible DUX4 expression that enables reproducible and synchronized experiments and validates the fidelity and FSHD relevance of multiple distinct models of DUX4 expression. Overall design: We performed a systematic comparison of DUX4-regulated changes in the transcriptome in our inducible codon-altered DUX4 expression system (iDUX4), the endogenous DUX4 expression system (enDUX4), and cells transduced with lentivirus constitutively expressing DUX4 (vDUX4). The specific datasets used in this comparison are as follows: iDUX4 represents a new dataset generated from the MB135 immortalized human myoblasts with the doxycycline inducible codon-altered DUX4 (iDUX4), performed in biological triplicate fourteen hours after DUX4 induction in growth media, with uninduced cells as a control; enDUX4 represents the published dataset of differentiated FSHD myocytes that do or do not express endogenous DUX4, as determined using a DUX4-responsive fluorescent reporter and flow sorting (9); vDUX4 represents a published dataset wherein two different myoblast cell lines (MB135 and 54-1) were transduced with a lentiviral construct that drives constitutive DUX4 expression via the PGK promoter and maintained in growth media for 24 hours (MB135) or 36 hours (54-1) prior to harvesting RNA.
Publication Title
Quantitative proteomics reveals key roles for post-transcriptional gene regulation in the molecular pathology of facioscapulohumeral muscular dystrophy.
Sample Metadata Fields
Specimen part, Treatment, Subject
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
Amplification of large chromosomal regions (gene amplification) is a common somatic alteration in human cancer cells and often is associated with advanced disease. A critical event initiating gene amplification is a DNA double strand break (DSB), which is immediately followed by the formation of a large DNA palindrome. Large DNA palindromes are frequent and non-randomly distributed in the genomes of cancer cells and facilitate further increase in copy number. Although the importance of the formation of large DNA palindromes as a very early event in gene amplification is widely recognized, it is not known 1) how a DSB is resolved to form a large DNA palindrome; and 2) whether any local DNA structure determines the location of large DNA palindromes. We show here that intra-strand annealing following a DNA double-strand break leads to the formation of large DNA palindromes and that DNA inverted repeats in the genome determines the efficiency of this event. Furthermore, in human Colo320DM cancer cells, a DNA inverted repeat in the genome marks the border between amplified and non-amplified DNA. Therefore, an early step of gene amplification is a regulated process that is facilitated by DNA inverted repeats in the genome.
Publication Title
Intrastrand annealing leads to the formation of a large DNA palindrome and determines the boundaries of genomic amplification in human cancer.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 21 Downloadable Samples
- Affymetrix Human Transcriptome Array 2.0 (hta20)
Description
In clinical trials assessing neoadjuvant androgen deprivation therapy plus next-generation androgen receptor axis inhibitors, a subset of patients fail to demonstrate a complete pathologic response following treatment and radical prostatectomy. We performed transcriptome analyses on laser capture microdissected foci of residual tumor from these patients.
Publication Title
Neoadjuvant-Intensive Androgen Deprivation Therapy Selects for Prostate Tumor Foci with Diverse Subclonal Oncogenic Alterations.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Mus musculus
- 24 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Genetic and epigenetic determinants of neurogenesis and myogenesis.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 24 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
The regulatory networks of differentiation programs have been partly characterized; however, the molecular mechanisms of lineage-specific gene regulation by highly similar transcription factors remain largely unknown. Here we compare the genome-wide binding and transcription profiles of NEUROD2-mediated neurogenesis with MYOD-mediated myogenesis. We demonstrate that NEUROD2 and MYOD bind a shared CAGCTG E-box motif and E-box motifs specific for each factor: CAGGTG for MYOD and CAGATG for NEUROD2. Binding at factor-specific motifs is associated with gene transcription, whereas binding at shared sites is associated with regional epigenetic modifications but not as strongly associated with gene transcription. Binding is largely constrained to E-boxes pre-set in an accessible chromatin context that determines the set of target genes activated in each cell type. These findings demonstrate that the differentiation program is genetically determined by E-box sequence whereas cell lineage epigenetically determines the availability of E-boxes for each differentiation program.
Publication Title
Genetic and epigenetic determinants of neurogenesis and myogenesis.
Sample Metadata Fields
Specimen part
View Samples- Danio rerio
- 12 Downloadable Samples
- Affymetrix Zebrafish Genome Array (zebrafish)
Description
Pbx homeodomain proteins have been implicated in the regulation of gene expression during muscle development. Whether Pbx proteins are required broadly for the regulation of muscle gene expression or are required for the expression of a specific subset of muscle gene expression is not known. We employed microarrays to determine the requirements for Pbx proteins during zebrafish development.
Publication Title
Pbx homeodomain proteins direct Myod activity to promote fast-muscle differentiation.
Sample Metadata Fields
No sample metadata fields
View Samples