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SRP148597
Homo sapiens
168 Downloadable Samples
Illumina HiSeq 4000, Illumina HiSeq 2500
Description
Knowledge of immune cell phenotypes in the tumor microenvironment is essential for understanding mechanisms of cancer progression and immunotherapy response. We created an immune map of breast cancer using single-cell RNA-seq data from 45,000 immune cells from eight breast carcinomas, as well as matched normal breast tissue, blood, and lymph node. We developed a preprocessing pipeline, SEQC, and a Bayesian clustering and normalization method, Biscuit, to address computational challenges inherent to single-cell data. Despite significant similarity between normal and tumor tissue-resident immune cells, we observed continuous phenotypic expansions specific to the tumor microenvironment. Analysis of paired single-cell RNA and T cell receptor (TCR) sequencing data from 27,000 additional T cells revealed the combinatorial impact of TCR utilization on phenotypic diversity. Our results support a model of continuous activation in T cells and do not comport with the macrophage polarization model in cancer, with important implications for characterizing tumor-infiltrating immune cells. Overall design: Single-cell RNA sequencing was performed on eight donors using the InDrop v2 protocol. For each donor populations of CD45+ immune cells were assayed for trancriptome-wide RNA-sequence. At least one replicate was taken for each donor.
Publication Title
Single-Cell Map of Diverse Immune Phenotypes in the Breast Tumor Microenvironment.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 29 Downloadable Samples
- NextSeq 500, Illumina HiSeq 2500
Description
Knowledge of immune cell phenotypes in the tumor microenvironment is essential for understanding mechanisms of cancer progression and immunotherapy response. We created an immune map of breast cancer using single-cell RNA-seq data from 45,000 immune cells from eight breast carcinomas, as well as matched normal breast tissue, blood, and lymph node. We developed a preprocessing pipeline, SEQC, and a Bayesian clustering and normalization method, Biscuit, to address computational challenges inherent to single-cell data. Despite significant similarity between normal and tumor tissue-resident immune cells, we observed continuous phenotypic expansions specific to the tumor microenvironment. Analysis of paired single-cell RNA and T cell receptor (TCR) sequencing data from 27,000 additional T cells revealed the combinatorial impact of TCR utilization on phenotypic diversity. Our results support a model of continuous activation in T cells and do not comport with the macrophage polarization model in cancer, with important implications for characterizing tumor-infiltrating immune cells. Overall design: Single-cell RNA sequencing was performed on three patients using the 10x genomics TCR profiling kits. For each patient, populations of T-cells were assayed for both TCR sequence and trancriptome-wide RNA-sequence. Two donors have a replicate experiment.
Publication Title
Single-Cell Map of Diverse Immune Phenotypes in the Breast Tumor Microenvironment.
Sample Metadata Fields
Specimen part, Subject
View Samples- Rattus norvegicus
- 4 Downloadable Samples
Affymetrix Rat Genome 230 2.0 Array (rat2302)
Description
The gene expression profling between Control and 300 mg/kg PhIP treatment in ventral prostate lobe of male F344 rats
Publication Title
Early detection of prostate carcinogens by immunohistochemistry of HMGB2.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 5 Downloadable Samples
Affymetrix Human Transcriptome Array 2.0 (hta20), Agilent-028004 SurePrint G3 Human GE 8x60K Microarray (Probe Name Version)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Functional analysis of the TRIB1 associated locus linked to plasma triglycerides and coronary artery disease.
Sample Metadata Fields
Cell line
View Samples- Drosophila melanogaster
- 6 Downloadable Samples
- Affymetrix Drosophila Genome 2.0 Array (drosophila2)
Description
The phagocytic elimination of cells undergoing apoptosis is an evolutionarily conserved innate immune mechanism for eliminating unnecessary cells. Previous studies showed an increase in the level of engulfment receptors in phagocytes after the phagocytosis of apoptotic cells, which leads to the enhancement of their phagocytic activity. However, precise mechanisms underlying this phenomenon require further clarification. We found that the pre-incubation of a Drosophila phagocyte cell line with the fragments of apoptotic cells enhanced the subsequent phagocytosis of apoptotic cells, accompanied by an augmented expression of the engulfment receptors Draper and integrin PS3. The DNA-binding activity of the transcription repressor Tailless was transiently raised in those phagocytes, depending on two partially overlapping signal-transduction pathways for the induction of phagocytosis as well as the occurrence of engulfment. The RNAi knockdown of tailless in phagocytes abrogated the enhancement of both phagocytosis and engulfment receptor expression. Furthermore, the hemocyte-specific RNAi of tailless reduced apoptotic cell clearance in Drosophila embryos. Taken together, we propose the following mechanism for the activation of Drosophila phagocytes after an encounter with apoptotic cells: two partially overlapping signaltransduction pathways for phagocytosis are initiated; transcription repressor Tailless is activated; expression of engulfment receptors is stimulated; and phagocytic activity is enhanced. This phenomenon most likely ensures the phagocytic elimination of apoptotic cells that stimulated phagocytes find thereafter and is thus considered as a mechanism to prime phagocytes in innate immunity.
Publication Title
Signaling pathway for phagocyte priming upon encounter with apoptotic cells.
Sample Metadata Fields
Cell line, Treatment, Time
View Samples- Homo sapiens
- 5 Downloadable Samples
- Affymetrix Human Transcriptome Array 2.0 (hta20), Agilent-028004 SurePrint G3 Human GE 8x60K Microarray (Probe Name Version)
Description
Objective - The TRIB1 locus has been linked to hepatic triglyceride metabolism in mice and to plasma triglycerides and coronary artery disease (CAD) in humans. The lipid associated SNPs identified by genome-wide association studies (GWAS) are located ~ 30 kb downstream from TRIB1 suggesting complex regulatory effects on genes or pathways relevant to hepatic triglyceride metabolism. The goal of this study was to investigate the functional relationship between common SNPs at the TRIB1 locus and plasma lipid traits.
Publication Title
Functional analysis of the TRIB1 associated locus linked to plasma triglycerides and coronary artery disease.
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 10 Downloadable Samples
- Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
Ewing Sarcoma is caused by a pathognomonic genomic translocation that places an N-terminal EWSR1 gene in approximation with one of several ETS genes (typically FLI1). This aberration, in turn, alters the transcriptional regulation of more than five hundred genes and perturbs a number of critical pathways that promote oncogenesis, cell growth, invasion, and metastasis. Among them, translocation-mediated up-regulation of the insulin-like growth factor receptor 1 (IGF-1R) and mammalian target of rapamycin (mTOR) are of particular importance since they work in concert to facilitate IGF-1R expression and ligand-induced activation, respectively, of proven importance in ES transformation. When used as a single agent in Ewing sarcoma therapy, IGF-1R or mTOR inhibition leads to rapid counter-regulatory effects that blunt the intended therapeutic purpose. Therefore, identify new mechanisms of resistance that are used by Ewing sarcoma to evade cell death to single-agent IGF-1R or mTOR inhibition might suggest a number of therapeutic combinations that could improve their clinical activity.
Publication Title
IGF-1R and mTOR Blockade: Novel Resistance Mechanisms and Synergistic Drug Combinations for Ewing Sarcoma.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 13 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
The genome of vertebrates contains endogenous retroviruses (ERVs) that have resulted from ancestral infections by exogenous retroviruses. ERVs are germline encoded, transmitted in a Mendelian fashion and account for about 8% of the human and 9.9% of the murine genome, respectively1, 2. By spontaneous activation and reintegration ERVs may cause insertional mutagenesis and thus participate in the process of malignant transformation or progression of tumor growth3, 4. However, if the innate immune system is able to recognize and control ERVs has not yet been elucidated. Here we report that, in vitro, nucleic-acid sensing TLRs on dendritic cells are activated by retroviral RNA and DNA from infected cells in vitro. Infection of TLR competent wild type mice with murine leukemia virus (MuLV)-like ERV isolates results in non-canonical gene upregulation, independent of type I IFN. In vivo, TLR3, -7 and -9 triple deficient mice (TLR379-/-) and mice with non functional TLR3, 7 and 9 signaling due to a mutation in UNC93B develop spontaneous ERV-induced viremia. More importantly, in TLR379-/- mice ERV-induced viremia correlates with acute T cell lymphoblastic leukemia (T-ALL). Multiple independent TLR379-/- T cell leukemia lines produce infectious MuLV of endogenous origin. These cell lines display de novo retroviral integration into the Nup214 or Notch1 gene locus leading to gene dysregulation that is reminiscent of aberrant Nup214 and Notch1 expression in human T-ALLs5. Overall, our results demonstrate that in addition to their role in innate immune defense against exogenous pathogens, TLR3,-7, and -9 may be essential for the control of endogenous retroviral mediated T-cell lymphomagenesis.
Publication Title
Nucleic acid-sensing Toll-like receptors are essential for the control of endogenous retrovirus viremia and ERV-induced tumors.
Sample Metadata Fields
Specimen part
View Samples- Oryza sativa
- 6 Downloadable Samples
- Affymetrix Rice Genome Array (rice)
Description
During an incompatible or compatible interaction between rice (Oryza sativa) and the Asian rice gall midge (Orseolia oryzae), a lot of genetic reprogamming occurs in the plant host
Publication Title
Metabolic and transcriptomic changes induced in host during hypersensitive response mediated resistance in rice against the Asian rice gall midge.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 960 Downloadable Samples
- Illumina HumanRef-8 v3.0 expression beadchip
Description
Statins reduce cardiovascular disease risk by lowering plasma low density lipoprotein (LDL)-cholesterol. To identify novel pathways that modulate statin response, we assessed the influence of simvastatin exposure on expression quantitative trait locus (eQTL) associations across the genome in 480 lymphoblastoid cell lines (LCLs). Cell lines were derived blood samples collected ant entry visit from participants in the Cholesterol and Pharmacogenomics (CAP) trial, who underwent a 6 week 40mg/day simvastatin trial. We identified 4590 cis-eQTLS that were independent of treatment status (FDR=1%) and six cis-eQTLS for which there was evidence of an interaction with treatment (FDR=20%). Genotypes and Phenotypes derived from these indivudals are available through dbGaP (Accession Number). eQTL results are available at: http://eqtl.uchicago.edu/cgi=bin/gbrowse/eqtl/
Publication Title
HNRNPA1 regulates HMGCR alternative splicing and modulates cellular cholesterol metabolism.
Sample Metadata Fields
Sex, Subject
View Samples