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SRP111408
Mus musculus
8 Downloadable Samples
Illumina HiSeq 2500
Description
Abstract: Choline is an essential nutrient and methyl donor required for epigenetic regulation. Here, we assess the impact of gut microbial choline metabolism on bacterial fitness and host biology by engineering a microbial community to lack a single choline-utilizing enzyme. Our results indicate that choline-utilizing bacteria compete with the host for this nutrient, significantly impacting plasma and hepatic levels of methyl-donor metabolites recapitulating biochemical signatures of choline deficiency. Mice harboring high levels of choline-consuming bacteria show increased susceptibility to metabolic disease. Furthermore, bacterially-induced reduction of methyl-donor availability alters global DNA methylation patterns in both adult mice and their offspring in utero and engenders anxious behavior. Altogether, our results reveal an underappreciated aspect of bacterial choline metabolism (i.e., methyl-donor depletion) that is linked to alterations in metabolism, epigenetics, and behavior. More broadly, this work suggests that interpersonal differences in microbial metabolism should be considered when determining optimal levels of nutrient intake. Overall design: 8 samples in total (biological n=4 per for each defined community; 9kw old female C57BL/6 mouse liver; 2 weeks of colonization and maintenance on 1% choline diet; 4hours of fasting prior to sacrifice)
Publication Title
Metabolic, Epigenetic, and Transgenerational Effects of Gut Bacterial Choline Consumption.
Sample Metadata Fields
Cell line, Subject
View Samples- Homo sapiens
- 18 Downloadable Samples
Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Studies of gene expression profiles using the whole genome wide microarray analysis in SUM149PT cells (ER-, p53mut) and SUM190PT cells (ER-, p53mut) when treated with 5 or 7.5 M CG-1521 alone and in combination with 10 nM 17-Estradiol. Comparisons between each treatment group provides evidence for the dysregulation of genes associated with the spindle assembly checkpoint.
Publication Title
Histone deacetylase inhibitors modulate miRNA and mRNA expression, block metaphase, and induce apoptosis in inflammatory breast cancer cells.
Sample Metadata Fields
Cell line
View Samples- Rattus norvegicus
- 6 Downloadable Samples
- Affymetrix Rat Genome 230 2.0 Array (rat2302)
Description
UMR106-01 osteoblastic cells are a model for studying bone mineralization. We have shown that mineralization is temporally synchronized within cultures grown under defined conditions . Cells are plated at time zero and differentiate into osteoblastic phenotype by 64 h later. If an exogenous phosphate source is added to the cultures, the cells form and deposit hydroxyapatite mineral within distinct extracellular supramolecular lipid protein complexes termed biomineralization foci (BMF) starting 12 h later. Mineralization is largely complete by 24 h later (88 h after plating). We have also shown that AEBSF, covalent serine protease inhibitor, blocks mineralization within BMF and inhibits the fragmentation of several proteins related to biomineralization. The present experiment was designed to test whether AEBSF treatment for 12 h has an effect on transcription by UMR106-01 osteoblastic cells. AEBSF is known to inactivate several serine proteases including SKI-1 (site 1, subtilisin kexin protease-1).SKI-1 functions intracellularly to activate transmembrane bound transcription factor precursors releasing the transcriptionally active N-terminal portions to imported into the nucleus. Thus, if AEBSF blocks transcription of mineralization related genes, it would support a role for SKI-1 in gene regulation in mineralizing UMR106-01 osteoblastic cells.
Publication Title
Inhibition of proprotein convertase SKI-1 blocks transcription of key extracellular matrix genes regulating osteoblastic mineralization.
Sample Metadata Fields
Cell line
View Samples- Rattus norvegicus
- 12 Downloadable Samples
- Affymetrix Rat Gene 1.0 ST Array (ragene10st)
Description
Crosstalk between Aryl hydrocarbonreceptor (AHR) and Estrogen receptor (ER) is poorly understood, but seems to play a major role in female reproductive organs.
Publication Title
Cross-Talk in the Female Rat Mammary Gland: Influence of Aryl Hydrocarbon Receptor on Estrogen Receptor Signaling.
Sample Metadata Fields
Sex, Specimen part
View Samples- Homo sapiens
- 4 Downloadable Samples
- Affymetrix Human Gene 2.0 ST Array (hugene20st)
Description
Type I low-grade gliomas (LGGs), characterized by 1p/19q co-deletions and IDH1/2 mutations, show superior overall survival compared to other gliomas. Approximately 70% of cases harbour mutations in the Capicua (CIC) gene, whose product is a transcriptional repressor whose transcriptional network has yet to be extensively studied in human cells. To address this, we developed CIC knockout cell lines and used transcriptome analyses to study the consequences of CIC loss. Results were further compared to data for Type I LGGs and stomach adenocarcinomas from The Cancer Genome Atlas (TCGA). We find that CIC appears to regulate the expression of genes involved in cell-cell adhesion and nervous system development. CIC deficiency is also found to be associated with a MEK activation transcriptional signature and to act as an effector of MEK signalling. Loss of CIC may thus present a novel mechanism for the dysregulation of this and other oncogenic pathways.
Publication Title
Comparative transcriptome analysis of isogenic cell line models and primary cancers links capicua (CIC) loss to activation of the MAPK signalling cascade.
Sample Metadata Fields
Cell line
View Samples- Rattus norvegicus
- 18 Downloadable Samples
- Illumina HiSeq 2500
Description
Purpose: identification of mRNAs that are potential targets of miR-203 in the endometrium and endometrial carcinoma Methods: mRNA profiles of three batches of wild-type (WT) and three independently generated miR-203 knockout (miR-203 KO) RUCA-I cells were produced by deep sequencing, using Illumina HiSeq 2500. The sequence reads that passed quality filters were analyzed at the transcript isoform level with TopHat followed by Cufflinks. Results: Using an optimized data analysis workflow, we mapped between 30 and 50 million sequence reads per sample to the rat genome (build rn6) and identified 26751 transcripts of which 1591 are differentially expressed in WT and miR-203 KO cells (p<0.05). Overall design: mRNA profiles of three WT batches and three independently generated miR-203 KO RUCA-I rat endometrial adenocarcinoma cell lines were produced by deep sequencing, using Illumina HiSeq2500.
Publication Title
Role of miR-203 in estrogen receptor-mediated signaling in the rat uterus and endometrial carcinoma.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 12 Downloadable Samples
- Affymetrix Human Exon 1.0 ST Array [transcript (gene) version (huex10st)
Description
The gene expression pathways leading to muscle pathology in facioscapulohumeral dystrophy (FSHD) remain to be elucidated. This muscular dystrophy is caused by a contraction of an array of tandem 3.3-kb repeats (D4Z4) at 4q35.2. We compared expression of control and FSHD myoblasts and myotubes (three preparations each) on exon microarrays (Affymetrix Human Exon 1.0 ST) and validated FSHD-specific differences for representative genes by qRT-PCR on additional myoblast cell strains. The FSHD and control myoblasts used for these experiments were shown to grow and differentiate into myotubes equally efficiently as control myoblasts. There were no significant FSHD-control differences in RNA levels for MYOD1 and MYOG at the myoblast and myotube stages and for MYF5 and MYF6 at the myoblast stage. In contrast, 295 other genes were dysregulated at least 2-fold in FSHD vs. control myoblasts (p <0.01, adjusted for multiple comparisons).
Publication Title
Gene expression during normal and FSHD myogenesis.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 28 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Thrombospondin 1 (TSP-1) is an anti-angiogenic matricellular protein with regulatory functions in inflammation and cancer. The type 1 repeats (TSR) domains of TSP-1 have been shown to interact with a wide range of proteins that result in the anti-angiogenic and anti-tumor properties of TSP-1. To evaluate potential therapeutic effects of TSRs in inflammatory bowel disease, we conducted clinical, histological and gene microarray analyses on a mouse model of induced colitis.
Publication Title
Thrombospondin-1 type 1 repeats in a model of inflammatory bowel disease: transcript profile and therapeutic effects.
Sample Metadata Fields
Specimen part
View Samples- Rattus norvegicus
- 12 Downloadable Samples
- Affymetrix Rat Gene 1.0 ST Array (ragene10st)
Description
Examination of crosstalk between Aryl hydrocarbonreceptor (AHR) and Estrogen receptor (ER) in the rat uterus on the level of mRNA transcriptome
Publication Title
Effects of the aryl hydrocarbon receptor agonist 3-methylcholanthrene on the 17β-estradiol regulated mRNA transcriptome of the rat uterus.
Sample Metadata Fields
Sex, Specimen part, Treatment
View Samples- Homo sapiens
- 10 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Pompe disease is caused by autosomal recessive mutations in the GAA gene, which encodes acid alpha-glucosidase. Although enzyme replacement therapy has recently improved patient survival greatly, the results in skeletal muscles and for advanced disease are still not satisfactory. Here, we report the derivation of Pompe disease induced pluripotent stem cells (PomD-iPSCs) and their potential for pathogenesis modeling, drug testing and disease marker identification. PomD-iPSCs maintained pluripotent features, and had low GAA activity and high glycogen content. Cardiomyocyte-like cells (CMLCs) differentiated from PomD-iPSCs recapitulated the hallmark Pompe disease pathophysiological phenotypes, including high levels of glycogen, abundant intracellular LAMP-1- or LC3-positive granules, and multiple ultrastructural aberrances. Drug rescue assessment showed that exposure of PomD-iPSC-derived CMLCs to rhGAA reversed the major pathologic phenotypes. Further, L-carnitine and 3- methyladenine treatment reduced defective cellular respiration and buildup of phagolysosomes, respectively, in the diseased cells. By comparative transcriptome analysis, we identified glycogen metabolism, lysosome and mitochondria related marker genes whose expression robustly correlated with the therapeutic effect of drug treatment in PomD-iPSC-derived CMLCs. Collectively, these results demonstrate that PomD-iPSCs are a promising in vitro disease model for development of novel therapeutic strategies for Pompe disease.
Publication Title
Human Pompe disease-induced pluripotent stem cells for pathogenesis modeling, drug testing and disease marker identification.
Sample Metadata Fields
Specimen part
View Samples