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GSE37563
Mus musculus
6 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
CTLA-4 is thought to inhibit effector T cells both intrinsically, by competing with CD28 for B7 ligands, and extrinsically, through the action of regulatory T cells. We studied in vivo responses of normal and CTLA-4-deficient antigen-specific murine effector CD4+ T cells. In order to do these studies in a physiological model of immunity to foreign antigen, we transferred small numbers of congenically marked RAG2-deficient 5C.C7 T cells with either a normal or knockout allele of CTLA-4 into normal syngeneic B10.A recipient mice. The T cells were then activated by immunization with MCC peptide and LPS. To look for transcriptional signatures of negative regulation of T cell responses by CTLA-4, we used microarray analysis to compare transcripts in wild type and CTLA-4 KO 5C.C7 T cells four days after immunization. This is the first instance in which differences are observed in extent of accumulation of wild type and CTLA-4 KO 5C.C7 T cells.
Publication Title
Cutting edge: CTLA-4 on effector T cells inhibits in trans.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Genome 430A 2.0 Array (mouse430a2)
Description
We used microarrays to determine how the quality and quantity of peptide-MHC impact TCR-induced gene expression in vivo.
Publication Title
Distinct influences of peptide-MHC quality and quantity on in vivo T-cell responses.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 30 Downloadable Samples
Illumina Genome Analyzer IIx
Description
Vertebrate ancestors had only cone-like photoreceptors. The duplex retina evolved in jawless vertebrates with the advent of highly photosensitive rod-like photoreceptors. Despite cones being the arbiters of high-resolution color vision, rods emerged as the dominant photoreceptor in mammals during a nocturnal phase early in their evolution. We investigated the evolutionary and developmental origins of rods in two divergent vertebrate retinae. In mice, we discovered genetic and epigenetic vestiges of short wavelength cones in developing rods and cell lineage tracing validated the genesis of rods from S-cones. Curiously, rods did not derive from S-cones in zebrafish. Our study illuminates several questions regarding the evolution of duplex retina and supports the hypothesis that, in mammals, the S-cone lineage was recruited via the Maf-family transcription factor NRL to augment rod photoreceptors. We propose that this developmental mechanism allowed the adaptive exploitation of scotopic niches during the nocturnal bottleneck early in mammalian evolution. Overall design: GFP positive cells from Nrlp-GFP or Nrlp-GFP;Nrl-KO mouse retinas at post-natal ages P2, P4, P6, P10, P14, and P28 were isolated by flow sorting by FACSAria II (Becton Dickinson). Total RNA was extracted by Trizol LS (Life Technologies) and analyzed by 2100 Bioanalyzer (Agilent Technologies Genomics). High quality of total RNA (RIN: >7.0) was subjected to sequencing library construction using 20 ng of total RNA as input. Libraries were constructed using a stranded modification of the Illumina TruSeq mRNA (Brooks, et al. Meth Mol Biol 2012). Each library was single-end sequenced in an independent lane of a GAIIx at a length of 76 bases. Fastq files were generated from reads passing chastity filter.
Publication Title
Recruitment of Rod Photoreceptors from Short-Wavelength-Sensitive Cones during the Evolution of Nocturnal Vision in Mammals.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Mus musculus
- 4 Downloadable Samples
- Illumina HiSeq 2000, Illumina HiSeq 2500
Description
Bptf, a component of NURF chromatin-remodeling complex, is essential for maintaining the pool size and function of hematopoietic stem cells (HSCs). Genome-wide transcriptome profiling revealed that Bptf loss caused down-regulation of HSC-specific gene-expression programs, which included master transcription factors (such as Meis1, Pbx1, and Lmo2) known to be required for HSC maintenance and self-renewal. Bptf directly bound to the promoter of 'stemness' TF genes, potentiating their transcription and DNA accessibility. Overall design: To dissect the gene-regulatory role of Bptf in HSPCs, we sorted out phenotypically identical LSK cells from the bone marrow of Bptf conditional KO mice and littermate controls, followed by ACAT-seq and RNA-seq studies. We also performed H3K4me3 ChIP-seq using HPC7 cells, a murine HSPC-mimicking cell line.
Publication Title
The Chromatin Remodeler BPTF Activates a Stemness Gene-Expression Program Essential for the Maintenance of Adult Hematopoietic Stem Cells.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Homo sapiens
- 8 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Epigenetic coordination of signaling pathways during the epithelial-mesenchymal transition.
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 8 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
TGFbeta/TNFalpha treated spheroid A549 cultures are a model of the epithelial-mesenchymal transition (EMT). These experiments capture the changes in global gene expression that result from cells being induced to undergo EMT (3D control vs 3D treated), but also the differences in gene expression when A549 is grown in spheroid cultures (2D control vs 3D untreated). EMT is efficiently induced only in the spheroid culture model.
Publication Title
Epigenetic coordination of signaling pathways during the epithelial-mesenchymal transition.
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 110 Downloadable Samples
- Affymetrix Human Genome U95A Array (hgu95a)
Description
Insulin is a potent pleiotropic hormone that affects processes such as cellular growth, differentiation, apoptosis, ion flux, energy expenditure, and carbohydrate, lipid, and protein metabolism.
Publication Title
The effect of insulin on expression of genes and biochemical pathways in human skeletal muscle.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 18 Downloadable Samples
- Illumina HiSeq 4000
Description
Immune checkpoint blockade is able to achieve durable responses in a subset of patients, however we lack a satisfying comprehension of the underlying mechanisms of anti-CTLA-4 and anti-PD-1 induced tumor rejection. To address these issues we utilized mass cytometry to comprehensively profile the effects of checkpoint blockade on tumor immune infiltrates in human melanoma and murine tumor models. These analyses reveal a spectrum of tumor infiltrating T cell populations that are highly similar between tumor models and indicate that checkpoint blockade targets only specific subsets of tumor infiltrating T cell populations. Anti-PD-1 predominantly induces the expansion of specific tumor infiltrating exhausted-like CD8 T cell subsets. In contrast, anti-CTLA-4 induces the expansion of an ICOS+ Th1-like CD4 effector population in addition to engaging specific subsets of exhausted-like CD8 T cells. Thus, our findings indicate that anti-CTLA-4 and anti-PD-1 checkpoint blockade induced immune responses are driven by distinct cellular mechanisms. Overall design: RNA profiles of a subset of tumor infiltrating T cell populations in anti-PD-1, anti-CTLA-r and control mice were generated by RNA sequencing, using Illumina HiSeq 4000. Mouse mutation background was assessed by whole exome sequencing data
Publication Title
Distinct Cellular Mechanisms Underlie Anti-CTLA-4 and Anti-PD-1 Checkpoint Blockade.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
B7x (B7-H4 or B7S1) is the seventh member of the B7 family and the in vivo function remains largely unknown. Despite new genetic data linking the B7x gene with autoimmune diseases, how exactly it contributes to peripheral tolerance and autoimmunity is unclear. Here we showed that B7x protein was not detected on antigen-presenting cells or T cells in both human and mice, which is unique in the B7 family. As B7x protein is expressed in some peripheral cells such as pancreatic b cells, we utilized a CD8 T cell-mediated diabetes model (AI4ab) in which CD8 T cells recognize an endogenous self-antigen, and found that mice lacking B7x developed more severe diabetes than control AI4ab mice. Conversely, mice overexpressing B7x in the b cells (Rip-B7xAI4ab) were diabetes free. Furthermore, adoptive transfer of effector AI4ab CD8 T cells induced diabetes in control mice, but not in Rip-B7xAI4ab mice. Mechanistic studies revealed that pathogenic effector CD8 T cells were capable of migrating to the pancreas but failed to robustly destroy tissue when encountering local B7x in Rip-B7xAI4ab mice. Although AI4ab CD8 T cells in Rip-B7xAI4ab mice and AI4ab mice showed similar cytotoxic function, cell death, and global gene expression profiles, these cells had greater proliferation in AI4ab mice than in RIP-B7xAI4ab mice. These results suggest that B7x in nonlymphoid organs prevents peripheral autoimmunity partially through inhibiting proliferation of tissue-specific CD8 T cells and that local overexpression of B7x on pancreatic b cells is sufficient to abolish CD8 T cell-induced diabetes.
Publication Title
B7x in the periphery abrogates pancreas-specific damage mediated by self-reactive CD8 T cells.
Sample Metadata Fields
Specimen part, Disease
View Samples- Homo sapiens
- 8 Downloadable Samples
- Illumina HiSeq 2500
Description
We sorted CD4 T cells from patients with metastatic melanoma at baseline and after three doses of ipilimumab. Overall design: We examined the differential expression of epigenetic enzymes
Publication Title
Modulation of EZH2 expression in T cells improves efficacy of anti-CTLA-4 therapy.
Sample Metadata Fields
Specimen part, Subject
View Samples