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SRP017340
Mus musculus
4 Downloadable Samples
Illumina Genome Analyzer II
Description
An autochthonous model of pancreatic ductal adenocarcinoma (PDA) permitted the analysis of why immunotherapy is ineffective in this human disease. Despite finding that PDA-bearing mice had cancer cell-specific CD8+ T cells, the mice, like human PDA patients, did not respond to two immunological checkpoint antagonists that promote the function of T cells, a-CTLA-4 and a-PD-L1. Immune control of PDA growth was achieved, however, by depleting carcinoma-associated fibroblasts (CAFs) that express Fibroblast Activation Protein (FAP). The depletion of the FAP+ stromal cell also uncovered the anti-tumor effects of a-CTLA-4 and a-PD-L1, indicating that its immune suppressive activity accounts for the failure of these T cell checkpoint antagonists. Three findings suggested that CXCL12 explained the overriding immunosuppression by the FAP+ cell: T cells were absent from regions of the tumor containing cancer cells; cancer cells were coated with the chemokine, CXCL12; and the FAP+ CAF was the principle source of CXCL12 in the tumor. Administering AMD3100, a CXCL12 receptor (CXCR4) inhibitor, induced rapid T cell accumulation among cancer cells, and acted synergistically with a-PD-L1 to selectively and greatly diminish cancer cells, identified by their loss-of-heterozygosity (LOH) of Trp53. The residual tumor was comprised only of pre-malignant epithelial cells and inflammatory cells. Thus, a single protein, CXCL12, from a single stromal cell type, the FAP+ CAF, may direct tumor immune evasion in a model of human PDA. Overall design: FAP+ cells were sorted from pancreatic ductal adenocarcinoma. Cells were isolated in duplicate experiments and these were analysed separately. These were compared separately to previously published publicly available CD4+ T-cell subset data (C57BL/6 mice and Foxp3-RFP mice (Line 8374) GEO accession GSE20898), and previously published FAP+ cell datasets (transgenic albino (Tyr-/-) C57BL/6 mouse, GEO accession GSE39438).
Publication Title
Targeting CXCL12 from FAP-expressing carcinoma-associated fibroblasts synergizes with anti-PD-L1 immunotherapy in pancreatic cancer.
Sample Metadata Fields
Specimen part, Disease, Disease stage, Subject
View Samples- Mus musculus
- 34 Downloadable Samples
- Illumina HiSeq 2500
Description
To provide further insight to the signaling pathways deregulated by SPOP mutation and determine the relevance of these models to human prostate cancer, we performed RNA-seq on SPOP mutant organoids and controls. RNA-seq reads mapped to human and mouse SPOP confirmed appropriate expression of the F133V transgenic transcript without overexpression compared to endogenous mouse Spop. Quantification of gene expression was performed via RSEQtools using GENCODE as reference gene–annotation set. Both SPOPmut and SPOPwt were done in the same run. S0 was done in first run; S1 and S2 were done in second run. S3, S4 and S5 were done in third run. S5mut and S5wt were excluded from differentially expressed genes analysis, due to the different mouse line. Overall design: Differentially expressed genes between mouse SPOPmut organoids and control by RNA-seq.
Publication Title
SPOP Mutation Drives Prostate Tumorigenesis In Vivo through Coordinate Regulation of PI3K/mTOR and AR Signaling.
Sample Metadata Fields
Specimen part, Subject
View Samples- Mus musculus
- 8 Downloadable Samples
- Illumina Genome Analyzer II
Description
Fibroblast activation protein-a (FAP) identifies stromal cells of mesenchymal origin in human cancers and chronic inflammatory lesions. In mouse models of cancer, they have been shown to be immune suppressive, but studies of their occurrence and function in normal tissues have been limited. With a transgenic mouse line permitting the bioluminescent imaging of FAP(+) cells, we find that they reside in most tissues of the adult mouse. FAP(+) cells from three sites, skeletal muscle, adipose tissue, and pancreas, have highly similar transcriptomes, suggesting a shared lineage. FAP(+) cells of skeletal muscle are the major local source of follistatin, and in bone marrow they express Cxcl12 and KitL. Experimental ablation of these cells causes loss of muscle mass and a reduction of B-lymphopoiesis and erythropoiesis, revealing their essential functions in maintaining normal muscle mass and hematopoiesis, respectively. Remarkably, these cells are altered at these sites in transplantable and spontaneous mouse models of cancer-induced cachexia and anemia. Thus, the FAP(+) stromal cell may have roles in two adverse consequences of cancer: their acquisition by tumors may cause failure of immunosurveillance, and their alteration in normal tissues contributes to the paraneoplastic syndromes of cachexia and anemia. Overall design: FAP+ cells were sorted from two mesenchymal tissues, visceral adipose and skeletal muscle, and from an epithelial organ, the pancreas. These were compared to MEFs. Cells were isolated in duplicate experiments and these were analysed separately. These were compared to previously published publically available CD4+ T-cell subset data.
Publication Title
Depletion of stromal cells expressing fibroblast activation protein-α from skeletal muscle and bone marrow results in cachexia and anemia.
Sample Metadata Fields
Specimen part, Subject
View Samples- Mus musculus
- 12 Downloadable Samples
Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
How neurons are wired to form precise circuits is crucial to understand the development of cortical functions. Glutamatergic pyramidal cell and GABAergic interneuron wire up the cortex through differentiated cellular events. However, little is known about the molecular mechanisms that underlie the unique features of interneuron wiring.
Publication Title
The Microtubule Regulator NEK7 Coordinates the Wiring of Cortical Parvalbumin Interneurons.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 24 Downloadable Samples
- Illumina HiSeq 2500, Illumina HiSeq 2000
Description
Mouse sinoatrial node transcriptome
Publication Title
RNA sequencing of mouse sinoatrial node reveals an upstream regulatory role for Islet-1 in cardiac pacemaker cells.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 18 Downloadable Samples
- Illumina HiSeq 2000
Description
Purpose: Aim of the study is to identify changes in hepatic gene expression induced by either a 40kcal% coconut oil rich high fat diet (HFD), a 40kcal% soybean oil plus coconut oil high fat diet (SO-HFD) or a low fat vivarium chow diet (Viv). Methods: Livers from mice that had been fed one of the above mentioned diets for 35 weeks, were used to make cDNA libraries that were then sent for deep sequencing, using the Illumina TruSeq RNA. Result: Many genes involved in metabolism, lipid binding, transport and storage and many Cyp genes are dysregulated in the two high fat diets as compared to Viv HFDs in SO-HFD mice. Comparing the two HFDs shows more metabolism and disease related genes dysregulated in SO-HFD vs HFD. Conclusion: A diet high in soybean oil may be more detrimental to metabolic health than a diet high in saturated fats. Overall design: cDNA isolated from livers from mice fed HFD, SO-HFD or Viv for 35 weeks, were 50bp pair-ended sequenced in triplicate using Illumina TruSeq RNA Sample Prep v2 Kit.
Publication Title
Soybean Oil Is More Obesogenic and Diabetogenic than Coconut Oil and Fructose in Mouse: Potential Role for the Liver.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 10 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
It is unknown how soon the diaphragm begins to start the process of atrophy following the start of MV. We hypothesized that genes responsible for maintaining diaphragmatic contractile function, stress response, energy transduction would be altered over the course of a 5 hour cardiothoracic surgery.
Publication Title
Gene expression changes in the human diaphragm after cardiothoracic surgery.
Sample Metadata Fields
Sex, Age
View Samples- Homo sapiens
- 16 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Through employing a comparative transcriptomics approach, we identified IRF1 as differentiatlly regulated between primary and in vitro derived genetically matched adipocytes.
Publication Title
Activation of IRF1 in Human Adipocytes Leads to Phenotypes Associated with Metabolic Disease.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 15 Downloadable Samples
- Illumina HiSeq 4000
Description
For placental mammals, the transition from the in utero maternal environment to postnatal life requires the activation of thermogenesis to maintain their core temperature. This is primarily accomplished by induction of uncoupling protein 1 (UCP1) in brown and beige adipocytes, the principal sites for uncoupled respiration. Despite its importance, how placental mammals license their thermogenic adipocytes to participate in postnatal uncoupled respiration is not known. Here, we provide evidence that the 'alarmin' IL-33, a nuclear cytokine that activates type 2 immune responses, licenses brown and beige adipocytes for uncoupled respiration. We find that, in absence of IL-33 or ST2, beige and brown adipocytes develop normally but fail to express an appropriately spliced form of Ucp1 mRNA, resulting in absence of UCP1 protein, and impairment in uncoupled respiration and thermoregulation. Together, these data suggest that IL-33 and ST2 function as a developmental switch to license thermogenesis during the perinatal period. Overall design: mRNA profiles of brown adipose tissues and inguinal white adipose tissues from postnatal day 0.5 and 24, respectively, WT and IL-33 knockout mice.
Publication Title
Perinatal Licensing of Thermogenesis by IL-33 and ST2.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 49 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
To better characterize the role of whole pericardial adipose tissue (PCAT) in the pathogenesis of disease, we performed a large-scale unbiased analysis of the transcriptional differences between pericardial and subcutaneous adipose tissue, analysing 53 microarrays across 19 individuals.
Publication Title
Pattern specification and immune response transcriptional signatures of pericardial and subcutaneous adipose tissue.
Sample Metadata Fields
Specimen part, Subject
View Samples