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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
- 7 Downloadable Samples
Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
We used microarrays to study the effect of Chd1 loss of function in mouse ES cells.
Publication Title
Chd1 regulates open chromatin and pluripotency of embryonic stem cells.
Sample Metadata Fields
Cell line
View Samples- Mus musculus
- 18 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Several aspects common to a Western lifestyle, including obesity and decreased physical activity, are known risks for gastrointestinal cancers. There is an increasing amount of evidence suggesting that diet profoundly affects the composition of the intestinal microbiota. Moreover, there is now unequivocal evidence linking a dysbiotic gut to cancer development. Yet, the mechanisms through which high-fat diet (HFD)-mediated changes in the microbial community impact the severity of tumorigenesis in the gut, remain to be determined.
Publication Title
High-fat-diet-mediated dysbiosis promotes intestinal carcinogenesis independently of obesity.
Sample Metadata Fields
Sex, Age, Specimen part, Treatment
View Samples- Mus musculus
- 9 Downloadable Samples
- Illumina HiSeq 2000
Description
Whether inflammatory macrophages can adopt features of the tissue resident niche and what mechanisms mediate phenotypic conversion remain unclear. In this study, we show by cell surface phenotyping, as well as by RNA-Seq transcriptional profiling and ATAC-Seq open chromatin regions profiling, that inflammatory monocyte can adopt a tissue resident phenotype, which is also accompanied by re-programming of the transcriptional profiles and remodeling of the open chromatin landscape. The conversion process is dependent on Vitamin A, suggesting that Vitamin A deficiency may lead to the failure to resolve inflammation, as inflammatory macrophages accumulate without adopting a tissue residency phenotype. Overall design: Monocyte-derived (N=3), tissue converted (N=3) and tissue resident (N=3) mouse peritoneal macrophages were FACS-sorted for RNASeq and ATACSeq.
Publication Title
Vitamin A mediates conversion of monocyte-derived macrophages into tissue-resident macrophages during alternative activation.
Sample Metadata Fields
Specimen part, Subject
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Gene 2.0 ST Array (mogene20st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Genome-Nuclear Lamina Interactions Regulate Cardiac Stem Cell Lineage Restriction.
Sample Metadata Fields
Specimen part, Cell line, Treatment
View Samples
GSE97753- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Gene 2.0 ST Array (mogene20st)
Description
Progenitor cells require coordinated expression of lineage-specific programs, and the nuclear lamina has emerged as an important scaffold for organizing chromatin in many cell types. These transcriptome profiling experiments accompany a study focused on defining nuclear organization changes during cardiac development. This dataset defines gene expression changes induced by Hdac3 deletion during early stages of cardiogenesis, modeled using ESC differentiation assays.
Publication Title
Genome-Nuclear Lamina Interactions Regulate Cardiac Stem Cell Lineage Restriction.
Sample Metadata Fields
Cell line, Treatment
View Samples- Homo sapiens
- 22 Downloadable Samples
- Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Integrative genomics identifies molecular alterations that challenge the linear model of melanoma progression.
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 22 Downloadable Samples
- Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
The two most common melanoma histopathologic subtypes, superficial spreading (SSM) and nodular melanoma (NM), are believed to represent sequential phases of linear progression from radial to vertical growth. Studies suggest, however, that SSM and NM are biologically distinct. We utilized an integrative genomic approach to examine the possibility that SSM and NM are the result of independent pathways characterized by unique molecular alterations. Cell lines including SSM, NM, metastatic melanoma, and melanocyte controls were evaluated for copy number changes and differential mRNA expression using single nucleotide polymorphism array (SNP 6.0, Affymetrix) and gene array (U133A 2.0, Affymetrix). Data sets were integrated to identify copy number alterations that correlated with gene expression, and array results were validated using immunohistochemistry on human tissue microarrays (TMAs) and an external data set. The functional effect of genomic deletion was assessed by lentiviral overexpression. Integrative genomics revealed 8 genes in which NM/SSM-specific copy number alterations were correlated with NM/SSM differential gene expression (P<0.05, Spearmans rank). Pathways analysis of differentially expressed genes (N=114) showed enrichment for metabolic-related processes. SSM-specific genomic deletions (DIS3, MTAP, G3BP2, SEC23IP, USO1) were verified in an expanded panel of cell lines, and forced overexpression of MTAP in SSM resulted in reduced cell growth. Metabolism-related gene ALDH7A1 was verified as overexpressed in NM using human TMAs.The identification of recurrent genomic deletions in SSM not present in NM challenges the linear model of melanoma progression and supports the unique molecular classification of SSM and NM.
Publication Title
Integrative genomics identifies molecular alterations that challenge the linear model of melanoma progression.
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 28 Downloadable Samples
- Affymetrix Human Exon 1.0 ST Array [transcript (gene) version (huex10st)
Description
Alternative mRNA splicing is an important mechanism for regulation of gene expression. Changes in gene expression contribute to the pathogenesis of heart failure. However, changes in mRNA splicing have not been systematically examined in heart disease. We hypothesized that mRNA splicing is changed in diseased hearts.
Publication Title
Heart failure-associated changes in RNA splicing of sarcomere genes.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 13 Downloadable Samples
- IlluminaHiSeq2000
Description
Synthetic DNA-binding proteins have found broad application in gene therapies and as tools for interrogating biology. Engineered proteins based on the CRISPR/Cas9 and TALE systems have been used to alter genomic DNA sequences, control transcription of endogenous genes, and modify epigenetic states. Although the activity of these proteins at their intended genomic target sites have been assessed, the genome-wide effects of their action have not been extensively characterized. Additionally, the role of chromatin structure in determining the binding of CRISPR/Cas9 and TALE proteins to their target sites and the regulation of nearby genes is poorly understood. Characterization of the activity these proteins using modern high-throughput genomic methods would provide valuable insight into the specificity and off-target effects of CRISPR- and TALE-based genome engineering tools. We have analyzed the genome-wide effects of TALE- and CRISPR-based transcriptional activators targeted to the promoters of two different endogenous human genes in HEK293T cells using a variety of high-throughput DNA sequencing methods. In particular, we assayed the DNA-binding specificity of these proteins and their effects on the epigenome. DNA-binding specificity was evaluated by ChIP-seq and RNA-seq was used to measure the specificity of these activators in perturbing the transcriptome. Additionally, DNase-seq was used to identify the chromatin state at target sites of the synthetic transcriptional activators and the genome-wide chromatin remodeling that occurs as a result of their action. Our results show that these genome engineering technologies are highly specific in both binding to their promoter target sites and inducing expression of downstream genes when multiple activators bind to a single promoter. Moreover, we show that these synthetic activators are able to induce the expression of silent genes in heterochromatic regions of the genome by opening regions of closed chromatin and decreasing DNA methylation. Interestingly, the transcriptional activation domain was not necessary for DNA-binding or chromatin remodeling in these regions, but was critical to inducing gene expression. This study shows that these CRISPR- and TALE-based transcriptional activators are exceptionally specific. Although we detected limited binding of off-target sites in the genome and changes to genome structure, these off-target event did not lead to any detectable changes in gene regulation. Collectively, these results underscore the potential for these technologies to make precise changes to gene expression for gene and cell therapies or fundamental studies of gene function. Overall design: HEK293T cells were transfected in triplicate with plasmids expressing synthetic transcription factors. The synthetic TFs were either (a) dCas9-VP64 fusion protein and a targeting guide RNA (gRNA), or (b) a TALE-VP64 fusion protein engineered to bind to a specific target site in the genome. As a control, cells were transfected with plasmids expressing GFP. After transfection, RNA-seq was used to identify both on-target and off-target binding sites for the synthetic TFs. The data in this submission were generated using the TALE transfection experiments.
Publication Title
Genome-wide specificity of DNA binding, gene regulation, and chromatin remodeling by TALE- and CRISPR/Cas9-based transcriptional activators.
Sample Metadata Fields
No sample metadata fields
View Samples