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SRP116020
Mus musculus
43 Downloadable Samples
Illumina HiSeq 2500
Description
Mice with a congenital Snord116 deletion model aspects of the Prader-Willi Syndrome. In this study, we examine the gene expression changes in four hypothalamic nuclei across 24-hour food deprived versus ad libitum fed mice. Overall design: Using mice with paternal deletion of the Snord116 cluster, we laser-captured microdissected four hypothalamic nuclei for RNA sequencing: the ventromedial hypothalamus (VMH), arcuate nucleus (ARC), dorsomedial hypothalamus (DMH) and paraventricular nucleus (PVN). Samples were taken from male mice in either the fed or 24-hour fasted state.
Publication Title
Hypothalamic loss of Snord116 recapitulates the hyperphagia of Prader-Willi syndrome.
Sample Metadata Fields
Cell line, Subject
View Samples- Mus musculus
- 15 Downloadable Samples
Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Obesity-associated insulin resistance is characterized by a state of chronic, low-grade inflammation that is associated with the accumulation of M1 proinflammatory macrophages in adipose tissue. Although different evidence explains the mechanisms linking the expansion of adipose tissue and adipose tissue macrophage (ATM) polarization, in the current study we investigated the concept of lipid-induced toxicity as the pathogenic link that could explain the trigger of this response. We addressed this question using isolated ATMs and adipocytes from genetic and diet-induced murine models of obesity. Through transcriptomic and lipidomic analysis, we created a model integrating transcript and lipid species networks simultaneously occurring in adipocytes and ATMs and their reversibility by thiazolidinedione treatment. We show that polarization of ATMs is associated with lipid accumulation and the consequent formation of foam celllike cells in adipose tissue. Our study reveals that early stages of adipose tissue expansion are characterized by M2-polarized ATMs and that progressive lipid accumulation within ATMs heralds the M1 polarization, a macrophage phenotype associated with severe obesity and insulin resistance. Furthermore, rosiglitazone treatment, which promotes redistribution of lipids toward adipocytes and extends the M2 ATM polarization state, prevents the lipid alterations associated with M1 ATM polarization. Our data indicate that the M1 ATM polarization in obesity might be a macrophage-specific manifestation of a more general lipotoxic pathogenic mechanism. This indicates that strategies to optimize fat deposition and repartitioning toward adipocytes might improve insulin sensitivity by preventing ATM lipotoxicity and M1 polarization.
Publication Title
Differential lipid partitioning between adipocytes and tissue macrophages modulates macrophage lipotoxicity and M2/M1 polarization in obese mice.
Sample Metadata Fields
Specimen part
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- Homo sapiens
- 7 Downloadable Samples
- Affymetrix Human Exon 1.0 ST Array [probe set (exon) version (huex10st)
Description
U1 small nuclear (sn)RNA, required for splicing of pre-mRNA, is encoded by genes on chromosome 1p36. Imperfect copies of these true (t)U1 snRNA genes, located on chromosome 1q12-21, were thought to be pseudogenes. However, many of these variant (v)U1 snRNA genes produce fully-processed transcripts that are packaged into potentially functional particles. Using antisense oligonucleotides, we have achieved functional knockdown of a specific vU1 snRNA in HeLa cells and identified over 400 transcriptome changes following interrogation of the Affymetrix Human Exon ST 1.0 array.
Publication Title
Differentially expressed, variant U1 snRNAs regulate gene expression in human cells.
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 70 Downloadable Samples
- Illumina HiSeq 2000
Description
Gene expression levels of pancreatic cell lines Overall design: RNA was extracted from cell lines and subjected to 50bp paired-end RNA sequencing
Publication Title
Integrated Patient-Derived Models Delineate Individualized Therapeutic Vulnerabilities of Pancreatic Cancer.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 2 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
We report a highly-penetrant form of obesity, initially observed in 31 heterozygous carriers of a 593kb or larger deletion at 16p11.2 from amongst subjects ascertained for cognitive deficits. Nineteen similar deletions were identified from GWAS data in 16053 individuals from 8 European cohorts; such deletions was absent from healthy non-obese controls and accounted for 0.7% of our morbid obesity cases (p = 6.4x10-8, OR = 43). These findings highlight a promising strategy for identifying missing heritability in obesity and other complex traits, in which insights from rare extreme cases can be used to elucidate the basis for more common phenotypes.
Publication Title
A new highly penetrant form of obesity due to deletions on chromosome 16p11.2.
Sample Metadata Fields
Specimen part, Disease
View Samples- Homo sapiens
- 260 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Master regulators of FGFR2 signalling and breast cancer risk.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 125 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
Genome-wide association studies for breast cancer have identified over 80 different risk regions in the genome, with the FGFR2 locus consistently identified as the most strongly associated locus. However, we know little about the mechanisms by which the FGFR2 locus mediates risk or the pathways in which multiple risk loci may combine to cause disease. Here we use a systems biology approach to elucidate the regulatory networks operating in breast cancer and examine the role of FGFR2 in mediating risk. Using model systems we identify FGFR2-regulated genes and, combining variant set enrichment and eQTL analysis, show that these are preferentially linked to breast cancer risk loci. Our results support the concept that cancer-risk associated genes cluster in pathways
Publication Title
Master regulators of FGFR2 signalling and breast cancer risk.
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 71 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
Genome-wide association studies for breast cancer have identified over 80 different risk regions in the genome, with the FGFR2 locus consistently identified as the most strongly associated locus. However, we know little about the mechanisms by which the FGFR2 locus mediates risk or the pathways in which multiple risk loci may combine to cause disease. Here we use a systems biology approach to elucidate the regulatory networks operating in breast cancer and examine the role of FGFR2 in mediating risk. Using model systems we identify FGFR2-regulated genes and, combining variant set enrichment and eQTL analysis, show that these are preferentially linked to breast cancer risk loci. Our results support the concept that cancer-risk associated genes cluster in pathways
Publication Title
Master regulators of FGFR2 signalling and breast cancer risk.
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 46 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
Genome-wide association studies for breast cancer have identified over 80 different risk regions in the genome, with the FGFR2 locus consistently identified as the most strongly associated locus. However, we know little about the mechanisms by which the FGFR2 locus mediates risk or the pathways in which multiple risk loci may combine to cause disease. Here we use a systems biology approach to elucidate the regulatory networks operating in breast cancer and examine the role of FGFR2 in mediating risk. Using model systems we identify FGFR2-regulated genes and, combining variant set enrichment and eQTL analysis, show that these are preferentially linked to breast cancer risk loci. Our results support the concept that cancer-risk associated genes cluster in pathways
Publication Title
Master regulators of FGFR2 signalling and breast cancer risk.
Sample Metadata Fields
Cell line
View Samples