Filters
Technology
Platform
SRP068722
Homo sapiens
40 Downloadable Samples
NextSeq500
Description
We apply RNA-seq to limited populations of Innate Lymphoid Cells type 2 and type 3 (ILC2s and ILC3s, respectively) in human individuals infected with acute HIV in the FRESH study. We measured the whole transcriptome of ILC2s and ILC3s in both untreated (n=2) and ART treated (n=2) individuals over the course of infection, in order to compare these populations at key points during infection, namely: viral detection, peak viremia, and weeks past peak viremia (6-7 weeks post detection). Lacking true biological replicates, HIV- patients in the same study (n=9) were used as replicates to conduct Differential Expression (DE) analysis between time points in both ILC2s and ILC3s on a patient by patient basis. In untreated patients, ILC2s and ILC3s differentially expressed genes associated with apoptosis and cell death between peak viremia and viral detection, while ART treated patients' ILC2s and ILC3s demonstrated a mitigated response. Comparing 6-7 weeks after detection with peak viremia revealed a relative decrease in genes associated in cell death in untreated patients, while ART treated patients showed varied responses where several DE genes were associated with immune response. Overall design: RNA-seq of two Innate Lymphoid Cell populations in 2 HIV+ untreated patients, 2 HIV+ ART treated patients, and 9 HIV- patients (control, replicates).
Publication Title
Innate Lymphoid Cells Are Depleted Irreversibly during Acute HIV-1 Infection in the Absence of Viral Suppression.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 8 Downloadable Samples
- Illumina HiSeq 2500
Description
Growing evidence implicates the importance of glia, particularly astrocytes, in neurological and psychiatric diseases. Here, we describe a rapid and robust method for the differentiation of highly pure populations of astrocytes from human induced pluripotent stem cells (hiPSCs), via a neural progenitor cell (NPC) intermediate. Using this method, we generated hiPSC-derived astrocyte populations (hiPSC-astrocytes) from 42 NPC lines (derived from 30 individuals) with an average of ~90% S100ß-positive cells. Transcriptomic analysis demonstrated that the hiPSC-astrocytes are highly similar to primary human fetal astrocytes and characteristic of a non-reactive state. hiPSC-astrocytes respond to inflammatory stimulants, display phagocytic capacity and enhance microglial phagocytosis. hiPSC-astrocytes also possess spontaneous calcium transient activity. Our novel protocol is a reproducible, straightforward (single media) and rapid (<30 days) method to generate homogenous populations of hiPSC-astrocytes that can be used for neuron-astrocyte and microglia-astrocyte co-cultures for the study of neuropsychiatric disorders. Overall design: 6 hiPSC-derived astrocyte lines were generated. Total RNA were extracted from these hiPSC-astrocytes as well as 2 primary astrocyte lines and analyzed by RNA sequencing.
Publication Title
An Efficient Platform for Astrocyte Differentiation from Human Induced Pluripotent Stem Cells.
Sample Metadata Fields
Sex, Specimen part, Subject
View Samples- Homo sapiens
- 70 Downloadable Samples
Affymetrix Human Exon 1.0 ST Array [probe set (exon) version (huex10st)
Description
To test whether a genomic classifier (GC) predicts development of metastatic disease in patients treated with salvage radiation therapy (SRT) after radical prostatectomy (RP).
Publication Title
Utilization of a Genomic Classifier for Prediction of Metastasis Following Salvage Radiation Therapy after Radical Prostatectomy.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 7 Downloadable Samples
- IlluminaHiSeq2000
Description
Background: Although genome-wide association studies (GWAS) have identified hundreds of variants associated with risk of autoimmune and immune-related disorders (AID), our understanding of the diseases mechanisms is limited. In particular, more than 90% of the risk variants lie in non-coding regions, and almost 10% of these map to long non-coding RNA transcripts (lncRNAs). LncRNAs are known to show more cell-type specificity than protein-coding genes. Methods: In this study, we aimed to characterize lncRNAs and protein-coding genes located in loci associated with nine AID which have been well-defined by Immunochip analysis, by transcriptome analysis across seven peripheral blood leukocyte populations (granulocytes, monocytes, NK cells, B-cells, memory-T cells, naive CD4+ and naive CD8+ T-cells) and four cord blood derived T-helper cell populations (precursor, primary, polarized (Th1, Th2) T-helper cells). Results: We show that lncRNAs mapping to loci shared between AIDs are significantly enriched in immune cell types when compared to lncRNAs from the whole genome (a<0.005). We were not able to prioritize single cell types relevant for specific diseases, but we observed five cell types enriched (a<0.005) in five AID (NK cells for inflammatory bowel disease, juvenile idiopathic arthritis, primary biliary cirrhosis, psoriasis; memory-T and CD8+ T-cells in juvenile idiopathic arthritis, primary biliary cirrhosis, psoriasis, rheumatoid arthritis; Th0 and Th2 cells for inflammatory bowel disease, juvenile idiopathic arthritis, primary biliary cirrhosis, psoriasis, rheumatoid arthritis). Furthermore we show that co-expression analyses of lncRNAs and protein-coding genes can predict the signaling pathways in which these AID-associated lncRNAs are involved. Conclusions: The observed enrichment of lncRNA transcripts in AID loci implies an important role for lncRNAs in AID etiology and suggests that lncRNA genes should be studied in more detail to correctly interpret GWAS findings. The co-expression results strongly support a model in which the lncRNA and protein-coding genes function together in the same pathways. Overall design: 7 immune cell types
Publication Title
Expression profiles of long non-coding RNAs located in autoimmune disease-associated regions reveal immune cell-type specificity.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 10 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Luminal breast cancers express estrogen (ER) and progesterone (PR) receptors, and respond to endocrine therapies. However, some ER+PR+ tumors display intrinsic or acquired resistance, possibly related to PR. Two PR isoforms, PR-A and PR-B, regulate distinct gene subsets that may differentially influence tumor fate. A high PR-A:PR-B ratio is associated with poor prognosis and tamoxifen resistance. We speculate that excessive PR-A marks tumors that will relapse early. Here we address mechanisms by which PR-A regulate transcription, focusing on SUMOylation. We use receptor mutants and synthetic promoter/reporters to show that SUMOylation deficiency or the deSUMOylase SENP1 enhance transcription by PR-A, independent of the receptors dimerization interface or DNA binding domain. De-SUMOylation exposes the agonist properties of the antiprogestin RU486. Thus, on synthetic promoters, SUMOylation functions as an independent brake on transcription by PR-A. What about PR-A SUMOylation of endogenous human breast cancer genes? To study these, we used gene expression profiling. Surprisingly, PR-A SUMOylation influences progestin target genes differentially, with some upregulated, others downregulated, and others unaffected. Hormone-independent gene regulation is also PR-A SUMOylation dependent. Several SUMOylated genes were analyzed in clinical breast cancer database. In sum, we show that SUMOylation does not simply repress PR-A. Rather, it regulates PR-A activity in a target selective manner including genes associated with poor prognosis, shortened survival, and metastasis.
Publication Title
SUMOylation Regulates Transcription by the Progesterone Receptor A Isoform in a Target Gene Selective Manner.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Rattus norvegicus
- 4 Downloadable Samples
- Affymetrix Rat Genome 230 2.0 Array (rat2302)
Description
Psychological, psychosocial and physical stress are major risk factors, which enhance the development of sporadic late-onset Alzheimer`s disease. The chronic unpredictable mild stress model mimics those risk factors and triggers signs of neurodegeneration and neuropathological features of sporadic AD such as tau hyperphosphorylation and enhanced amyloid beta generation. The study investigated the impact of chronic unpredictable mild stress on signs of neurodegeneration by analyzing hippocampal gene expression with whole genome microarray gene expression profiling.
Publication Title
Inhibition of ACE Retards Tau Hyperphosphorylation and Signs of Neuronal Degeneration in Aged Rats Subjected to Chronic Mild Stress.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Mus musculus
- 9 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Steroid hormones regulate essential physiological processes and inadequate levels are associated with various pathological conditions. In testosterone-producing Leydig cells, steroidogenesis is strongly stimulated by LH via its receptor leading to increased cAMP production and expression of the steroidogenic acute regulatory (STAR) protein, which is essential for the initiation of steroidogenesis. Leydig cell steroidogenesis then passively decreases following the rapid degradation of cAMP into AMP by phosphodiesterases. In this study, we show that AMP-activated protein kinase (AMPK) is activated following cAMP breakdown in MA-10 and MLTC-1 Leydig cells. Activated AMPK then actively inhibits cAMP-induced steroidogenesis by repressing the expression of key regulators of steroidogenesis including Star and Nr4a1. Similar results were obtained in Y-1 adrenal cells and in the constitutive steroidogenic cell line R2C. Our data identify AMPK as an active repressor of steroid hormone biosynthesis in steroidogenic cells that is essential to preserve cellular energy and prevent excess steroid production.
Publication Title
A cell-autonomous molecular cascade initiated by AMP-activated protein kinase represses steroidogenesis.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Arabidopsis thaliana
- 24 Downloadable Samples
- Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)
Description
Powdery mildew, caused by the fungus Blumeria graminis (DC) Speer, is one of the most important foliar diseases of cereals worldwide. It is an obligate biotrophic parasite, colonising leaf epidermal cells to obtain nutrients from the plant cells without killing them. Syringolin A (sylA), a circular peptide secreted by the phytopathogenic bacterium Pseudomonas syringae pv. syringae, triggers a hypersensitive cell death reaction (HR) at infection sites when sprayed onto powdery mildew infected wheat which essentially eradicates the fungus. The rational was to identify genes whose expression was specifically regulated during HR, i.e. genes that might be involved in the switch of compatibility to incompatibility.<br></br>Powdery mildew-infected or uninfected plants were treated with syringolin two days after infection and plant material for RNA extraction was collected at 0.5, 1, 2, 4, 8, 12 hours after treatment (hat), resulting in an early (2 and 4 hat) and late pool (8 and 12 hat). Plant material that was uninfected prior to syringolin treatment was collected 8 and 12 hat (late pool of uninfected plant material), and 1 hat, respectively.
Publication Title
Transcriptional changes in powdery mildew infected wheat and Arabidopsis leaves undergoing syringolin-triggered hypersensitive cell death at infection sites.
Sample Metadata Fields
Compound, Time
View Samples- Rattus norvegicus
- 16 Downloadable Samples
- Affymetrix Rat Genome 230 2.0 Array (rat2302)
Description
The initial segment of the epididymis is vital for male fertility, therefore, it is important to understand the mechanisms that regulate this important region. Deprival of testicular luminal fluid factors/lumicrine factors from epididymis, a subset of cells within the initial segment undergo apoptosis. In this study, microarray analyses was used to examine early changes in the downstream signal transduction pathways following the loss of lumicrine factors, and we discovered the following cascade of events leading to loss of protection and eventual apoptosis. First, mRNA expression of several key components of ERK pathway decreased sharply after 6 hours of loss protection from testicular lumicrine factors. After 12 hours, the levels of mRNA expression of STAT and NF-B pathways components increased, mRNA expression of genes encoding cell cycle inhibitors increased. After 18 hours of loss protection from testicular lumicrine factors, apoptosis was observed in the initial segment. In conclusion, testicular lumicrine factors protect the cells of the initial segment by activating ERK pathway, repressing STAT and NF-B pathways, and preventing a cascade of reactions leading to apoptosis.
Publication Title
Testicular lumicrine factors regulate ERK, STAT, and NFKB pathways in the initial segment of the rat epididymis to prevent apoptosis.
Sample Metadata Fields
Sex, Specimen part, Time
View Samples- Homo sapiens
- 31 Downloadable Samples
- Illumina HiSeq 4000, Illumina HiSeq 2500
Description
Abstract: Cellular senescence, an integral component of aging and cancer, arises in response to diverse triggers, including telomere attrition, macromolecular damage, and signaling from activated oncogenes. At present, senescent cells are identified by the combined presence of multiple traits, such as senescence-associated protein expression and secretion, DNA damage, and ß-galactosidase activity; unfortunately, these traits are neither exclusively nor universally present in senescent cells. To identify robust shared markers of senescence, we have performed RNA-sequencing analysis across 8 diverse models of senescence triggered in human diploid fibroblasts (WI-38, IMR-90) and endothelial cells (HUVEC, HAEC) by replicative exhaustion, exposure to ionizing radiation or doxorubicin, and expression of the oncogene HRASG12V. The intersection of the altered transcriptomes revealed 47 RNAs consistently elevated and 26 RNAs consistently reduced across all senescence models, including many protein-coding mRNAs and some long noncoding RNAs. We propose that these shared transcriptome profiles will enable the identification of senescent cells in vivo, the investigation of their roles in aging and malignancy, and the development of strategies to target senescent cells therapeutically. Overall design: Transcriptomic analysis of various cell line models of senescence and their respective controls
Publication Title
Transcriptome signature of cellular senescence.
Sample Metadata Fields
Specimen part, Cell line, Treatment, Subject
View Samples