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SRP078918
Mus musculus
88 Downloadable Samples
Illumina HiSeq 2500
Description
Regulatory T (Treg) cells, expressing abundant amounts of the IL-2 receptor (IL-2R), are reliant on IL-2 produced by activated T cells. This feature implied a key role for a simple network based on IL-2 consumption by Treg cells in their suppressor function. However, congenital deficiency in IL-2R results in reduced expression of the Treg lineage specification factor Foxp3, confounding experimental efforts to understand the role of IL-2R expression and signaling in Treg suppressor function. Using genetic gain and loss of function approaches, we demonstrate that IL-2 capture is dispensable for control of CD4+ T cells, but is important for limiting CD8+ T cell activation, and that IL-2R dependent STAT5 transcription factor activation plays an essential role in Treg suppressor function separable from T cell receptor signaling. Overall design: Gene expression profiles in Treg cells with or without an expression of an active form of STAT5 were compared by RNA sequencing. Male 8-wk-old Foxp3Cre-ERT2Rosa26Stat5bCA (STAT5b-CA) and Foxp3Cre-ERT2 (control) mice, nine mice for each experimental group, received a single dose (4 mg) of tamoxifen by oral gavage 4 months before isolation. Splenic CD4+Foxp3(YFP/GFP)+GITRhiCD25hi Treg and CD4+Foxp3(YFP/GFP)-CD62LhiCD44lo T naive cells were double sorted using a BD FACSAria II cell sorter. The T cell subsets isolated from three individual mice in the same experimental group (genotype) was pooled into one biological replicate; three biological replicates were generated. A total of 12 samples, i.e., two genotypes, two cell cypes, and three replicates, was subjected to RNA-seq analysis. Samples were sequenced on the Illumina HiSeq 2500 to an average depth of 27.5 million 50-bp read pairs per sample.
Publication Title
Transcription factor Foxp1 regulates Foxp3 chromatin binding and coordinates regulatory T cell function.
Sample Metadata Fields
Sex, Specimen part, Subject
View Samples- Homo sapiens
- 250 Downloadable Samples
- Illumina HiSeq 2500, Ion Torrent Proton
Description
The goal of this study is to compare transcriptional profiles of regulatory T cells and conventional CD4 T cells in human breast cancer to regulatory T cells and conventional CD4 T cells in normal breast parenchyma and in peripheral blood. Overall design: RNA sequencing of 2 different cell types in 3 different tissues
Publication Title
Regulatory T Cells Exhibit Distinct Features in Human Breast Cancer.
Sample Metadata Fields
Specimen part, Subject
View Samples- 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- Homo sapiens
- 2 Downloadable Samples
Illumina HumanHT-12 V3.0 expression beadchip
Description
mRNA from bone marrow-derived MSCs stably expressing CTGF-specific shRNA (or empty vector control) was analyzed for differential gene expression. Significant differences were found in cell proliferation-related genes, especially genes related to the M phase of the cell cycle, which were down-regulated in CTGF-knockdown-MSCs compared to control MSCs.
Publication Title
Connective tissue growth factor regulates adipocyte differentiation of mesenchymal stromal cells and facilitates leukemia bone marrow engraftment.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 10 Downloadable Samples
- IlluminaHiSeq2500
Description
The role of post-transcriptional gene regulation in human brain development and cognitive diseases remains mostly uncharacterized. ELAV-like RNA binding proteins are a family of proteins that regulate several aspects of neuronal function including neuronal excitability and synaptic transmission. Here, we identify the downstream transcriptional networks of ELAVL2, an RNA-binding protein with unknown function in the brain. We knockdown expression of ELAVL2 in human neurons and conduct RNA-sequencing, identifying networks of differentially expressed and alternatively spliced genes with altered ELAVL2. These networks contain autism-relevant genes as well as previously identified targets of other RNA binding proteins implicated in autism spectrum disorders such as RBFOX1 and FMRP. ELAVL2-regulated coexpression networks are also enriched for synaptic genes as well as genes with human-specific patterns of gene expression in the frontal pole. Together, these data suggest that ELAVL2 regulation of transcript expression is critical for neuronal functions at risk in autism spectrum disorders and such mechanisms of post-transcriptional gene regulation may have contributed to human brain evolution. Overall design: We carried out RNA-sequencing (RNA-seq) of human neural progenitors cells. For the RNA-seq, 5 indipendent replicates were used for the neural progenitor cells. Primary human neural progenitor cultures were derived from mid-gestation fetal brain. Cells were transduced with a lentivirus containing a specific shRNA to ELAVL2 or a control shRNA. Cells were differentiated into neurons for 4 weeks and then harvested.
Publication Title
ELAVL2-regulated transcriptional and splicing networks in human neurons link neurodevelopment and autism.
Sample Metadata Fields
No sample metadata fields
View Samples- Macaca mulatta, Pan troglodytes, Homo sapiens
- 29 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Divergent whole-genome methylation maps of human and chimpanzee brains reveal epigenetic basis of human regulatory evolution.
Sample Metadata Fields
No sample metadata fields
View Samples- Macaca mulatta, Pan troglodytes, Homo sapiens
- 29 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
We identified human-specific gene expression patterns in the brain by comparing expression with chimpanzee and rhesus macaque
Publication Title
Divergent whole-genome methylation maps of human and chimpanzee brains reveal epigenetic basis of human regulatory evolution.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 9 Downloadable Samples
- Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
Hepatocytes are polarized epithelial cells whose function depends upon their ability to distinguish between the apical and basolateral surfaces that are located at intercellular tight junctions. It has been proposed that the signaling cascades that originate at these junctions influence cellular activity by controlling gene expression in the cell nucleus. To assess the validity of this proposal with regard to hepatocytes, we depleted expression of the tight junction protein junctional adhesion molecule-A (JAM-A) in the HepG2 human hepatocellular carcinoma cell line. Reduction of JAM-A resulted in a striking change in cell morphology, with cells forming single-layered sheets instead of the normal multi-layered clusters. In the absence of JAM-A, other tight junction proteins were mislocalized, and canaliculi, which form the apical face of the hepatocyte, were consequently absent. While most changes in gene expression were modest, there was a strong transcriptional induction of the adherens junction protein E-cadherin in cells with reduced levels of JAM-A. This increase in E-cadherin was partially responsible for the observed alterations in cell morphology and mislocalization of tight junction proteins. We therefore propose that we have uncovered a novel mechanism for crosstalk between specific components of tight and adherens junctions that can be utilized to regulate adhesion between hepatic cells and to maintain hepatocyte cell polarity.
Publication Title
Junctional adhesion molecule-A is critical for the formation of pseudocanaliculi and modulates E-cadherin expression in hepatic cells.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 11 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The availability of pluripotent stem cells offers the possibility of using such cells to model hepatic disease and development. With this in mind, we previously established a protocol that facilitates the differentiation of both human embryonic stem cells and induced pluritpotent cells into cells with hepatocyte characteristics. The use of highly defined culture conditions and the avoidance of feeder cells or embryoid bodies allowed synchronous and reproducible differentiation to occur. The differentiation toward a hepatocytelike fate appeared to recapitulate many of the stages normally associated with the formation of hepatocytes in vivo. In the current study we addressed the feasibility of using human pluripotent stem cells to probe the molecular mechanisms underlying human hepatocyte differentiation. We demonstrate i) that human ES cells express a number of mRNAs that characterize each stage in the differentiation process, ii) that gene expression can be efficiently depleted throughout the differentiation time course using shRNAs expressed from lentiviruses, and iii) that the nuclear hormone receptor HNF4a is essential for specification of human hepatic progenitor cells by establishing expression of the network of transcription factors that control hepatocyte cell fate.
Publication Title
HNF4A is essential for specification of hepatic progenitors from human pluripotent stem cells.
Sample Metadata Fields
Specimen part, Time
View Samples