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GSE15729
Mus musculus
15 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
The multi-ligand Receptor for AGE (RAGE) contributes to atherosclerosis in apolipoprotein (ApoE) null mice in both the non-diabetic and diabetic states. Previous studies using soluble RAGE, the extracellular ligand-binding domain of RAGE, or homozygous RAGE null mice showed that blockade or deletion of RAGE resulted in marked reduction in atherosclerotic lesion area and complexity compared to control animals. In parallel, significant down-regulation of inflammatory mediators and matrix metalloproteinases was evident in ApoE null mice aortas devoid of RAGE compared to those of ApoE null RAGE-expressing mice. Although these findings suggested that RAGE triggered pro-atherogenic mechanisms via regulation of inflammatory gene expression, these studies did not reveal the broader pathways by which RAGE contributed to atherosclerosis in ApoE null mice.
Publication Title
Activation of the ROCK1 branch of the transforming growth factor-beta pathway contributes to RAGE-dependent acceleration of atherosclerosis in diabetic ApoE-null mice.
Sample Metadata Fields
Sex, Age, Specimen part, Disease, Disease stage
View Samples- Schizosaccharomyces pombe
- 24 Downloadable Samples
- Affymetrix Yeast Genome 2.0 Array (yeast2)
Description
Analysis of histone acetyl transferases (HATs) from the MYST and GNAT families in S. pombe to identify functional differences or overlap with regard to gene expression. Mutations were made to Elp3 and Gcn5 (GNAT family), and to Mst2 (MYST family). Mutants showed distinct phenotypes which were repressed or enhanced by mutant combinations.
Publication Title
Expression profiling of S. pombe acetyltransferase mutants identifies redundant pathways of gene regulation.
Sample Metadata Fields
Cell line, Treatment
View Samples- Homo sapiens
- 16 Downloadable Samples
Illumina HiSeq 2000
Description
Sandhoff disease, one of the GM2 gangliosidoses, is a lysosomal storage disorder characterized by the absence of b-hexosaminidase A and B activity and the concomitant lysosomal accumulation of its substrate, GM2 ganglioside. It features catastrophic neurodegeneration and death in early childhood. How the lysosomal accumulation of ganglioside might affect the early development of the nervous system is not understood. Recently, cerebral organoids derived from induced pluripotent stem (iPS) cells have illuminated early developmental events altered by disease processes. To develop an early neurodevelopmental model of Sandhoff disease, we first generated iPS cells from the fibroblasts of an infantile Sandhoff disease patient, then corrected one of the mutant HEXB alleles in those iPS cells with CRISPR/Cas9 genome-editing technology, thereby creating isogenic controls. Next, we used the parental Sandhoff disease iPS cells and isogenic HEXB-corrected iPS cell clones to generate cerebral organoids that modeled the first trimester of neurodevelopment. The Sandhoff disease organoids but not the HEXB-corrected organoids accumulated GM2 ganglioside, and exhibited increased size and cellular proliferation compared with the HEXB-corrected organoids. Whole-transcriptome analysis demonstrated that development was impaired in the Sandhoff disease organoids, suggesting that alterations in neuronal differentiation may occur during early development in the GM2 gangliosidoses Overall design: Sandhoff disease and corrected cerebral organoids grown for 8 and 10 weeks were analyzed: four samples at each time point, each consisting of 4–6 pooled organoids, for both Sandhoff and corrected. Whole transcriptome from Sandhoff disease and corrected organoids for both time points were generated by deep sequencing on an Illumina HiSeq 2500.
Publication Title
Cerebral organoids derived from Sandhoff disease-induced pluripotent stem cells exhibit impaired neurodifferentiation.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 4 Downloadable Samples
- IlluminaHiSeq2000
Description
Epigenetic and metabolic reprogrammings are implicated in cancer progression with unclear mechanisms. We report here that the histone methyltransferase NSD2 drives cancer cell and tumor resistance to therapeutics such as tamoxifen, doxorubicin, and radiation by reprogramming of glucose metabolism. NSD2 coordinately up-regulates expression of TIGAR, HK2 and G6PD and stimulates pentose phosphate pathway (PPP) production of NADPH for ROS reduction. We discover that elevated expression of TIGAR, previously characterized as a fructose-2,6-bisphosphatase, is localized in the nuclei of resistant tumor cells where it stimulates NSD2 expression and global H3K36me2 mark. Mechanistically, TIGAR interacts with the antioxidant regulator Nrf2 and facilitates chromatin assembly of Nrf2-H3K4me3 methylase MLL1 and elongating Pol-II, independent of its metabolic enzymatic activity. In human tumors, high levels of NSD2 correlate strongly with early recurrence and poor survival and are associated with nuclear-localized TIGAR. This study defines a nuclear TIGAR-mediated, epigenetic autoregulatory loop functioning in redox rebalance for resistance to tumor therapeutics. Overall design: A total of 4 samples were analyzed in this study. The study included two cell lines, MCF7 and the tamoxifen-resistant subline TMR. Both were were cultured in medium containing vehicle control and/or 4-hydroxytamoxifen (Tam). The untreated MCF7 and TMR cell lines served as controls for the study.
Publication Title
Reprogramming metabolism by histone methyltransferase NSD2 drives endocrine resistance via coordinated activation of pentose phosphate pathway enzymes.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 16 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
The very low density lipoprotein receptor (VLDLR) is a multi-ligand receptor that mediates pleiotropic biological processes, such as brain development.
Publication Title
The very low density lipoprotein receptor attenuates house dust mite-induced airway inflammation by suppressing dendritic cell-mediated adaptive immune responses.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 134 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The complex milieu of inflammatory mediators associated with many diseases is often too dilute to directly measure in the periphery, necessitating development of more sensitive measurements suitable for mechanistic studies, earlier diagnosis, guiding selection of therapy, and monitoring interventions. Previously, we determined that plasma of recent-onset (RO) Type 1 diabetes (T1D) patients induce a proinflammatory transcriptional signature in fresh peripheral blood mononuclear cells (PBMC) relative to that of unrelated healthy controls (HC). Here, using an optimized cryopreserved PBMC-based protocol, we compared the signature found between unrelated healthy controls and non-diabetic cystic fibrosis patients possessing Pseudomonas aeruginosa pulmonary tract infection.
Publication Title
Identification of molecular signatures of cystic fibrosis disease status with plasma-based functional genomics.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 207 Downloadable Samples
- Illumina HiSeq 2000
Description
Yin and yang 1 (YY1) is a well-known zinc-finger transcription factor with crucial roles in normal development and malignancy. YY1 acts both as a repressor and an activator of gene expression. We have identified 23 individuals with de novo mutations or deletions of YY1 and phenotypic features that define a syndrome of cognitive impairment, behavioral alterations, intrauterine growth retardation, feeding problems, and various congenital malformations. Our combined clinical and molecular data define the 'YY1 syndrome' as a haploinsufficiency syndrome. Through immunoprecipitation of YY1-bound chromatin from person-derived cells, using antibodies recognizing both ends of the protein, we show that YY1 deletions and missense mutations lead to a global loss of YY1 binding, with a preferential retention at high-occupancy sites. Finally, we uncover a widespread loss of H3K27 acetylation in particular on the YY1-bound enhancers, underscoring a crucial role for YY1 in enhancer regulation. Collectively, these results define a clinical syndrome caused by haploinsufficiency of YY1 through dysregulation of key transcriptional regulators. Overall design: Individuals with mutations or deletion in YY1 were identified among patients with idiopathic intellectual disability. LCLs were established from 4 of these patients (1 deletion, 2 missense mutations, and 1 non-sense mutation undergoing non-sense-mediated decay) as well as from unrelated controls, and their transcriptome were compared.
Publication Title
YY1 Haploinsufficiency Causes an Intellectual Disability Syndrome Featuring Transcriptional and Chromatin Dysfunction.
Sample Metadata Fields
Specimen part, Subject
View Samples