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SRP118694
Homo sapiens
12 Downloadable Samples
Description
Innate immune memory is the phenomenon whereby innate immune cells such as monocytes or macrophages undergo functional reprogramming after exposure to microbial components. In this study, we apply epigenomic and transcriptomic analysis to a clinical trial of BCG vaccination in healthy adults. Overall design: Healthy volunteers were injected with the BCG vaccine, and monocytes were collected before vaccination, and 1 month after vaccination.
Publication Title
The role of Toll-like receptor 10 in modulation of trained immunity.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 12 Downloadable Samples
- Illumina HiSeq 2500
Description
We report RNA-sequencing data of 12 platelet samples isolated from four healthy individuals and incubated with either E. coli K12, E. coli O18 or no bacteria. This dataset highlights the differential effect of bacteria on spliced platelet RNA profiles. Overall design: Blood platelets were isolated from whole blood in citrate-coated BD Vacutainers by standard centrifugation and multiple washing steps. Total RNA was extracted from the platelet pellet, subjected to cDNA synthesis and SMARTer amplification, fragmented by Covaris shearing, and prepared for sequencing using the TruSeq Nano DNA Sample Preparation Kit. Subsequently, pooled sample libraries were sequenced on the Illumina HiSeq 2500 platform. All steps were quality-controlled using Bioanalyzer 2100 with RNA 6000 Picochip, DNA 7500 and DNA High Sensitivity chips measurements. For further downstream analyses, reads were quality-controlled using Trimmomatic, mapped to the human reference genome using STAR, and intron-spanning reads were summarized using HTseq.
Publication Title
Impact of Escherichia coli K12 and O18:K1 on human platelets: Differential effects on platelet activation, RNAs and proteins.
Sample Metadata Fields
Specimen part, Disease, Subject
View Samples- Homo sapiens
- 19 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
In order to understand the molecular mechanism behind Vulvar Intraepithelial Neoplasia (VIN), we have analyzed the gene expression profile of VIN lesions in comparison to controls.
Publication Title
HPV related VIN: highly proliferative and diminished responsiveness to extracellular signals.
Sample Metadata Fields
Sex
View Samples- Mus musculus
- 19 Downloadable Samples
- Illumina HiSeq 2000
Description
Piwi-interacting small RNAs (piRNAs) of fetal prospermatogonia of mice have been strongly implicated in transposon control. In contrast, little is known about biogenesis and function of abundant piRNAs from adult testes expressed in late spermatocytes and round spermatids. These so-called "pachytene" piRNAs are processed from long non-coding piRNA precursors and have no defined RNA targets in the transcriptome even though their binding partner Piwi, MIWI, is essential for spermiogenesis and fertility. Here we report that 129SvJae mice lacking Maelstrom (MAEL), a conserved piRNA pathway protein, exhibit spermiogenic arrest with defects in acrosome and flagellum formation. Further analysis revealed MAEL association with RNPs containing MIWI, TDRD6, and processed intermediates of pachytene piRNA precursors of various length. Loss of MAEL causes a 10-fold drop in pachytene piRNA levels but an increase in piRNAs from abundantly expressed mRNAs. These results suggest a MAEL-dependent mechanism for the selective processing of pachytene piRNA precursor into piRNAs. Strikingly, ribosome profiling of Mael-null testes revealed that reduced piRNA production is accompanied by reduced translation of over 800 spermiogenic mRNAs including those encoding acrosome and flagellum proteins. In light of recent reports of piRNA-independent protection of translationally repressed mRNPs by MIWI and piRNA-dependent turnover of MIWI, we propose that pachytene piRNAs function by controlling the availably of MIWI for the translational repression of spermiogenic mRNAs. Overall design: piRNA sequencing, RNA immunoprecipitation, and expression measurements (RNA-Seq and ribosome profiling) in wild-type and Mael -/- testes
Publication Title
Reduced pachytene piRNAs and translation underlie spermiogenic arrest in Maelstrom mutant mice.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Homo sapiens
- 13 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Profiling project of a panel of tubular adenoma and serrated adenoma patient material collected in the Academic Medical Center (AMC) in Amsterdam, The Netherlands. The aim of the study was to compare the expression profiles of different types of colon cancer precursor lesions (tubular versus serrated adenomas) and determine their correspondence with a set of colon cancer patient-derived profiles that have distinct clinical outcomes.
Publication Title
Poor-prognosis colon cancer is defined by a molecularly distinct subtype and develops from serrated precursor lesions.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 143 Downloadable Samples
- Illumina HiSeq 2500, Illumina HiSeq 2000
Description
Cancer-associated inflammatory processes in the tumour microenvironment, as well as systemically, are strongly linked with poor disease outcome in cancer patients. For most human solid tumour types, high systemic neutrophil-to-lymphocyte ratios (NLR) are associated with increased metastasis and poor overall survival and recent experimental studies have demonstrated a causal relationship between neutrophils and metastasis formation. However, to date, the cancer cell-intrinsic mechanisms dictating the substantial heterogeneity in systemic neutrophilic inflammation between tumour-bearing hosts are largely unresolved. Using a panel of 16 distinct genetically engineered mouse models (GEMMs) for breast cancer, we demonstrate that tumour cell-intrinsic loss of p53 changes the phenotype and function of macrophages in the microenvironment, leading to activation of a systemic inflammatory cascade that drives neutrophil expansion. Mechanistically, p53 loss in cancer cells induces secretion of Wnt ligands that act in a paracrine fashion to stimulate IL-1b production from tumour-associated macrophages. Intratumoural IL-1ß production stimulates an inflammatory cascade leading to the systemic accumulation of neutrophils. Pharmacological and genetic blockade of cancer cell-derived Wnt secretion reverses IL-1ß expression by macrophages and subsequent systemic neutrophilic inflammation. Collectively, using pre-clinical mouse models for breast cancer, we demonstrate a novel mechanistic link between loss of p53 in cancer cells, Wnt ligand secretion and systemic immune activation. This illustrates the importance of cancer cell-intrinsic genetic aberrations in dictating cancer-associated inflammation. These insights set the stage for personalized immune intervention strategies for cancer patients. Overall design: In this study, gene expression profiles of tumours from genetically engineered mouse models (GEMMs) were analysed using RNA sequencing. Analysis was performed on bulk tumours of 10 GEMMs with different tissue-specific mutations driving tumorigenesis, totalling to 125 different tumours (n=5 or more per group). Subsequently, samples were grouped according to p53 status of the tumour (models containing Trp53 floxed alleles, or not) and comparisons were made between p53-KO and p53-WT tumours.
Publication Title
Loss of p53 triggers WNT-dependent systemic inflammation to drive breast cancer metastasis.
Sample Metadata Fields
Cell line, Subject
View Samples- Homo sapiens
- 1 Downloadable Sample
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Primary colon CSC cultures were transduced with a Wnt responsive construct (TOP-GFP) and were single cell cloned. 10% highest and lowest TOP-GFP cell fractions were FACS sorted and arrayed.
Publication Title
Wnt activity defines colon cancer stem cells and is regulated by the microenvironment.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 4 Downloadable Samples
- IlluminaHiSeq2000
Description
Integrator (INT) is an RNA polymerase II (RNAPII)-associated complex that was recently identified to have a broad role in both RNA processing and transcription regulation. INT has at least 14 subunits, but INT germline mutations causing human disease have not been reported. We identified mutations in the Integrator Complex Subunit 8 gene (INTS8) causing a rare neurodevelopmental syndrome. In patient cells we identified significant disturbance of gene expression and RNA processing. Also, we show that injection of ints8 oligonucleotide morpholinos into zebrafish embryos leads to prominent underdevelopment of the head demonstrating the evolutionary conserved requirement of INTS8 in brain development. Overall design: RNA sequencing was carried out using RNA samples from fibroblasts from two individuals with germline bi-allelic INTS8 mutations and from two healthy individuals
Publication Title
Human mutations in integrator complex subunits link transcriptome integrity to brain development.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 298 Downloadable Samples
- Affymetrix Human Exon 1.0 ST Array [transcript (gene) version, custom CDF (huex10st)
Description
Four different molecular classifications of muscle-invasive bladder cancer (MIBC) based on gene expression have been proposed. With the ultimate goal of utilizing these molecular subtypes for personalized treatment, we investigated their significance in the context of neoadjuvant cisplatin-based chemotherapy (NAC).
Publication Title
Impact of Molecular Subtypes in Muscle-invasive Bladder Cancer on Predicting Response and Survival after Neoadjuvant Chemotherapy.
Sample Metadata Fields
Age, Disease, Disease stage, Treatment
View Samples- Homo sapiens
- 9 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The transcription factor Peroxisome Proliferator-Activated Receptor (PPAR) is an important regulator of hepatic lipid metabolism. While PPAR is known to activate transcription of numerous genes, no comprehensive picture of PPAR binding to endogenous genes has yet been reported. To fill this gap, we performed ChIP-chip in combination with transcriptional profiling on HepG2 human hepatoma cells treated with the PPAR agonist GW7647. We found that GW7647 increased PPAR binding to 4220 binding regions. GW7647-induced binding regions showed a bias around the transcription start site and most contained a predicted PPAR binding motif. Several genes known to be regulated by PPAR, such as ACOX1, SULT2A1, ACADL, CD36, IGFBP1 and G0S2, showed GW7647-induced PPAR binding to their promoter. A GW7647-induced PPAR-binding region was also assigned to SREBP-targets HMGCS1, HMGCR, FDFT1, SC4MOL, and LPIN1, expression of which was induced by GW7647, suggesting cross-talk between PPAR and SREBP signaling. Our data furthermore demonstrate interaction between PPAR and STAT transcription factors in PPAR-mediated transcriptional repression, and suggest interaction between PPAR and TBP and C/EBP in PPAR-mediated transcriptional activation. Overall, our analysis leads to important new insights into the mechanisms and impact of transcriptional regulation by PPAR in human liver and highlight the importance of cross-talk with other transcription factors.
Publication Title
Profiling of promoter occupancy by PPARalpha in human hepatoma cells via ChIP-chip analysis.
Sample Metadata Fields
Specimen part, Cell line, Treatment
View Samples