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SRP051737
Homo sapiens
7 Downloadable Samples
IlluminaHiSeq2500
Description
During activation, T cells integrate multiple signals from APCs and cytokine milieu. The blockade of these signals can have clinical benefits as exemplified by CTLA4-Ig, which blocks interaction of B7 co-stimulatory molecules on APCs with CD28 on T cells. Variants of CTLA4-Ig, abatacept and belatacept are FDA approved as immunosuppressive agents in arthritis and transplantation whereas murine studies suggested that CTLA4-Ig can be beneficial in a number of other diseases. However, detailed analysis of human CD4 cell hyporesponsivness induced by CTLA4-Ig has not been performed. Herein, we established a model to study effect of CTLA4-Ig on the activation of human naïve T cells in a human mixed lymphocytes system. Comparison of human CD4 cells activated in the presence or absence of CTLA4-Ig, showed that co-stimulation blockade during TCR activation does not affect NFAT signaling but results in decreased activation of NF-kB and AP-1 transcription factors followed by profound decrease in proliferation and cytokine production. The resulting T cells become hyporesponsive to secondary activation and, although capable of receiving TCR signals, fail to proliferate or produce cytokines, demonstrating properties of anergic cells. However, unlike some models of T cell anergy, these cells did not possess increased levels of TCR signaling inhibitor CBLB. Rather, the CTLA4-Ig induced hyporesponsiveness was associated with an elevated level of p27kip1 cyclin-dependent kinase inhibitor. Overall design: Time series. Human resting and activated T cell dUTP mRNA-Seq profiles were generated on Illumina HiSeq2500
Publication Title
Functional characterization of human T cell hyporesponsiveness induced by CTLA4-Ig.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 77 Downloadable Samples
Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
The molecular etiology of uterine leiomyosarcoma (ULMS) is poorly understood, which accounts for the wide disparity in outcomes among women with this disease. We examined and compared the molecular profiles of ULMS, fibroids, and normal myometrium (NL) to identify clinically relevant molecular subtypes. RNA was hybridized to Affymetrix U133A 2.0 transcription microarrays. Differentially expressed genes and pathways were identified using standard methods.
Publication Title
Molecular subtypes of uterine leiomyosarcoma and correlation with clinical outcome.
Sample Metadata Fields
Sex
View Samples- Homo sapiens
- 9 Downloadable Samples
- Illumina HiSeq 4000
Description
The development of CRISPR-Cas systems for targeting DNA and RNA in diverse organisms has transformed biotechnology and biological research. Moreover, the CRISPR revolution has highlighted bacterial adaptive immune systems as a rich and largely unexplored frontier for discovery of new genome engineering technologies. In particular, the class 2 CRISPR-Cas systems, which use single RNA-guided DNA-targeting nucleases such as Cas9, have been widely applied for targeting DNA sequences in eukaryotic genomes. Here, we report DNA-targeting and transcriptional control with class I CRISPR-Cas systems. Specifically, we repurpose the effector complex from type I variants of class 1 CRISPR-Cas systems, the most prevalent CRISPR loci in nature, that target DNA via a multi-component RNA-guided complex termed Cascade. We validate Cascade expression, complex formation, and nuclear localization in human cells and demonstrate programmable CRISPR RNA (crRNA)-mediated targeting of specific loci in the human genome. By tethering transactivation domains to Cascade, we modulate the expression of targeted chromosomal genes in both human cells and plants. This study expands the toolbox for engineering eukaryotic genomes and establishes Cascade as a novel CRISPR-based technology for targeted eukaryotic gene regulation. Overall design: Examination of transcriptome-wide changes in gene expression with Cascade-mediated activation of endogenous genes.
Publication Title
Targeted transcriptional modulation with type I CRISPR-Cas systems in human cells.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Mus musculus
- 4 Downloadable Samples
Description
Gametogenesis is dependent on the expression of germline-specific genes. However, it remains unknown how the germline epigenome is distinctly established from that of somatic lineages. Here we show that genes commonly expressed in somatic lineages and spermatogenesis-progenitor cells undergo repression in a genome-wide manner in late stages of the male germline and identify underlying mechanisms. SCML2, a germline-specific subunit of a Polycomb repressive complex 1 (PRC1), establishes the unique epigenome of the male germline through two distinct antithetical mechanisms. SCML2 works with PRC1 and promotes RNF2-dependent ubiquitination of H2A, thereby marking somatic/progenitor genes on autosomes for repression. Paradoxically, SCML2 also prevents RNF2-dependent ubiquitination of H2A on sex chromosomes during meiosis, thereby enabling unique epigenetic programming of sex chromosomes for male reproduction. Our results reveal divergent mechanisms involving a shared regulator by which the male germline epigenome is distinguished from that of the soma and progenitor cells. Overall design: RNA-seq and ChIP-seq analyses using wild-type and Scml2-KO spermatogenic cells
Publication Title
Poised chromatin and bivalent domains facilitate the mitosis-to-meiosis transition in the male germline.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 38 Downloadable Samples
- Affymetrix Human Gene 2.1 ST Array (hugene21st)
Description
Prevalence and severity of allergic diseases have increased worldwide. To date, respiratory allergy phenotypes are not fully characterized and, in addition, the mechanisms underlying sublingual immunotherapy (SLIT) are still unknown.
Publication Title
Exploring novel systemic biomarker approaches in grass-pollen sublingual immunotherapy using omics.
Sample Metadata Fields
Specimen part, Treatment, Time
View Samples- Homo sapiens
- 64 Downloadable Samples
- Illumina Genome Analyzer IIx, Illumina HiSeq 2500
Description
Septic shock is the most severe complication of sepsis, associated with high mortality. The patient's response to supportive therapy is very heterogeneous and the underlying mechanisms are still elusive. In order to identify which are the actors (genes and pathways) that play a role in establishing the response, we investigate the whole blood transcriptome in septic shock patients with positive and negative responses to early supportive hemodynamic therapy, assessed by changes in SOFA scores within the first 48 hours from ICU admission. We pinpointed genes and pathways that are differently modulated and enriched respectively within 48hrs between responders and non-responders. Overall design: We analyzed 31 patients (17 Responders and 14 Not Responders to early therapy). For each patient, 2 samples were collected. In particular the first sample (T1) collected within 16 hours from ICU admission whereas the second (T2) collected within 48 hours from ICU admission. Experimental groups (Responders and Not Responders) are defined accordingly with SOFA scores improvements within 48 hours.
Publication Title
Identification of a transcriptome profile associated with improvement of organ function in septic shock patients after early supportive therapy.
Sample Metadata Fields
Specimen part, Subject, Time
View Samples- Mus musculus
- 64 Downloadable Samples
- Affymetrix Mouse Gene 1.1 ST Array (mogene11st)
Description
The activation profiles of macrophages under different immune and inflammatory conditions have generated great interest. LPS, in particular, is a commonly used in vitro model of infection and inflammation studies in macrophages. We have used gene expression microarrays to define the effects of each of three variables; LPS dose, LPS vs. interferons beta and gamma, and genetic background on the transcriptional response of mouse bone marrow-derived macrophages
Publication Title
Analysis of the transcriptional networks underpinning the activation of murine macrophages by inflammatory mediators.
Sample Metadata Fields
No sample metadata fields
View Samples- Rattus norvegicus
- 30 Downloadable Samples
- Affymetrix Rat Genome 230 2.0 Array (rat2302)
Description
Temporal changes of gene expression from 1-wk- to 5-wk-old rat in kidney and lung, and the effect of prior growth inhibition on these genetic changes.
Publication Title
Coordinated postnatal down-regulation of multiple growth-promoting genes: evidence for a genetic program limiting organ growth.
Sample Metadata Fields
Age, Specimen part
View Samples- Rattus norvegicus
- 24 Downloadable Samples
- Affymetrix Rat Gene 1.1 ST Array (ragene11st)
Description
The purpose of this study was to investigate whether paternal high-fat diet (HFD) transgenerationally remodeled the hepatic transcriptome of F2 female rats
Publication Title
Paternal high-fat diet transgenerationally impacts hepatic immunometabolism.
Sample Metadata Fields
Sex, Specimen part
View Samples- Rattus norvegicus
- 18 Downloadable Samples
- Affymetrix Rat Gene 1.1 ST Array (ragene11st)
Description
The purpose of this study was to investigate whether grandpaternal high-fat diet (HFD) transgenerationally remodels the transcriptome of skeletal muscle
Publication Title
Grandpaternal-induced transgenerational dietary reprogramming of the unfolded protein response in skeletal muscle.
Sample Metadata Fields
Sex, Specimen part
View Samples