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GSE57589
Mus musculus
24 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Gut microbes elicit specific changes in gene expression in the colon of mice. We colonized germ-free mice with microbial communities from the guts of humans, zebrafish and termites, human skin and tongue, soil and estuarine microbial mats.
Publication Title
Bacteria from diverse habitats colonize and compete in the mouse gut.
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus
- 28 Downloadable Samples
Illumina HiSeq 2000
Description
Thymic Treg cells, mature non-Treg CD4+ single positive thymocytes, peripheral (spleen) resting and activated Treg cells were sorted from Foxp3-gfp reporter (wid type, WT) mice or Foxp3 enhancer CNS3 knockout (KO, carrying the same GFP reporter) mice. Total RNA was extracted and used for RNA sequencing to assess gene expression profiles. Overall design: Two 6-8 week old littermates of male Foxp3-gfp and Foxp3?CNS3-gfp mice were used to sort Treg cells and conventional CD4+ T cells. Lymphocyte preparation and electronic sorting were performed at the same time. RNA extraction, SMART amplification, library preparation were conducted in parallel.
Publication Title
A mechanism for expansion of regulatory T-cell repertoire and its role in self-tolerance.
Sample Metadata Fields
No sample metadata fields
View Samples- Sus scrofa
- 94 Downloadable Samples
- Illumina HiSeq 2500
Description
Chromatin packaging in sperm protects it against DNA fragmentation, and the importance of proper chromatin packaging for boar fertility outcome has become increasingly evident. Little is known however about the molecular mechanisms underlying differences in sperm DNA fragmentation and an understanding of the genes controlling this sperm parameter could help in selecting the best boars for AI use. The aim of this study was to identify differentially expressed genes in testis of Norsvin Landrace and Duroc boars with good and bad sperm DNA fragmentation using transcriptome sequencing and to use the data for polymorphism search. RNA sequence reads were obtained using Illumina technology and mapped by TopHat using the Ensembl pig database. Differentially expressed genes and pathways were analyzed using the R Bioconductor packages edgeR and goseq respectively. Using a false discovery rate of 0.05, 309 and 375 genes were found displaying significant differences in expression level between the good and bad condition in Landrace and Duroc respectively. Of the differentially expressed genes, 72 were found in common for the two breeds. Gene ontology analysis revealed that terms common for the two breeds included extracellular matrix, extracellular region and calcium ion binding. Additionally, different metabolic processes were enriched in Landrace and Duroc, whereas immune response ontologies were found to be important in Landrace. SNP detection in Landrace/Duroc identified 53182/53931 variants in 10924/10748 transcripts and of these, 1573/1827 SNPs occurred in 189/241 unique genes that were also differentially expressed. Possible high impact variants were detected using SnpEff. Transcriptome sequencing identified differentially expressed genes and nucleotide variants related to differences in sperm DNA fragmentation, and functional annotation of the genes pointed towards important biochemical pathways. This study provides insights into the genetic network underlying this trait and is a first step towards using sperm DNA fragmentation for predicting boar fertility. Overall design: Nine Landrace, five low and four high, and eleven Duroc, five low and six high, boars were selected for transcriptome profiling based on their extreme DFI values. The biological replicates within the high and low groups were compared.
Publication Title
RNA sequencing reveals candidate genes and polymorphisms related to sperm DNA integrity in testis tissue from boars.
Sample Metadata Fields
Subject
View Samples- Mus musculus
- 23 Downloadable Samples
- Illumina HiSeq 2000
Description
Human lung adenocarcinoma exhibits a propensity for de-differentiation, which complicates diagnosis and treatment, and predicts for poor overall patient survival. In genetically engineered mouse (GEM) models of lung cancer, expression of the BRAFV600E oncoprotein kinase initiates the growth of benign tumors that retain characteristics of their cell of origin, alveolar type II (ATII) pneumocytes. Cooperating genetic alterations such as silencing of the PTEN tumor suppressor or expression of mutationally-activated PI3-kinase-a (PIK3CAH1047R) promote malignant progression of such benign tumors to malignant adenocarcinoma, though their effects on differentiation status are unknown. To address this in vivo, we generated a new conditional BrafCAT allele in which Cre-mediated recombination leads to expression of a bi-cistronic mRNA encoding both BRAFV600E and the tdTomato fluorescent protein. Using this model, we demonstrate that coincident expression of BRAFV600E and PIK3CAH1047R in ATII pneumocytes leads to rapid and widespread cell de-differentiation. Surprisingly, the combined effects of BRAFV600E and PIK3CAH1047R on ATII pneumocyte identity occurred without loss of expression of the lung lineage transcription factors NKX2.1, FOXA1, or FOXA2. Instead, we demonstrate a novel role of PGC1a in maintaining pneumocyte identity, which is lost upon PIK3CAH1047R expression. These findings provide additional insight into how two of the most commonly mutated growth factor signaling pathways contribute to the pathogenesis of lung adenocarcinoma. Overall design: BRAFV600E mutant mouse lung adenocarcinoma (n=6) vs BRAFV600E;PIK3CAH1047R mutant lung adenocarcinoma (n= 8), and BRAFV600E;PGC1aHET (n=5) vs BRAFV600E;PGC1aNULL tumors (n=4)
Publication Title
Mutationally-activated PI3'-kinase-α promotes de-differentiation of lung tumors initiated by the BRAF<sup>V600E</sup> oncoprotein kinase.
Sample Metadata Fields
Sex, Specimen part, Subject
View Samples- Sus scrofa
- 48 Downloadable Samples
- Porcine Gene 1.1 ST Array (porgene11st)
Description
An early settlement of a complex gut microbiota can protect against gastro-intestinal dysbiosis, but the effects of neonatal microbiota colonization on the gut barrier upon the further encounter of favorable bacteria or not, are largely unknown.
Publication Title
Molecular networks affected by neonatal microbial colonization in porcine jejunum, luminally perfused with enterotoxigenic Escherichia coli, F4ac fimbria or Lactobacillus amylovorus.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Homo sapiens
- 28 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
We demonstrate the in vivo efficacy of the histone deacetylase inhibitor Panobinostat (LHB589) against MLL-rearranged ALL using xenograft mouse models of MLL-rearranged ALL cell lines and primary patient cells. Panobinostat monotherapy showed strong anti-leukaemic effects, extending survival and reducing overall disease burden. Comprehensive molecular analyses in vitro showed the anti-leukaemic activity in MLL-rearranged ALL to involve depletion of H2B ubiquitination via suppression of the RNF20/RNF40/WAC E3 ligase complex.
Publication Title
The HDAC inhibitor panobinostat (LBH589) exerts in vivo anti-leukaemic activity against MLL-rearranged acute lymphoblastic leukaemia and involves the RNF20/RNF40/WAC-H2B ubiquitination axis.
Sample Metadata Fields
Treatment
View Samples- Homo sapiens
- 24 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
We investigated the anti-leukemic effects of the Bromodomain and Extra Terminal inhibitor I-BET151 on primary MLL-AF4 patient samples, using a xenotransplantation mouse model of MLL+ infant ALL in vivo. We reported that I-BET151 treatment impairs the engraftment and the disease burden of primary MLL+ infant ALL samples transplanted into immunedeficient mice. I-BET151 is able to arrest the growth of leukemic cells by blocking cell division and rapidly inducing apoptosis, through the deregulation of crucial target genes of the BRD4 and HOXA9/HOXA7 network. Moreover I-BET151 sensitizes glucocorticoid-resistant MLL+ cells to Prednisolone. Finally we observed that I-BET151 treatment is even more efficient when used in combination with HDAC inhibitor.
Publication Title
Antileukemic Efficacy of BET Inhibitor in a Preclinical Mouse Model of MLL-AF4<sup>+</sup> Infant ALL.
Sample Metadata Fields
Treatment, Subject
View Samples- Homo sapiens
- 148 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The first in vitro tests for developmental toxicity made use of rodent cells. Newer teratology tests, e.g. developed during the ESNATS project, use human cells and measure mechanistic endpoints (such as transcriptome changes). However, the toxicological implications of mechanistic parameters are hard to judge, without functional/morphological endpoints. To address this issue, we developed a new version of the human stem cell-based test STOP-tox(UKN). For this purpose, the capacity of the cells to self-organize to neural rosettes was assessed as functional endpoint: pluripotent stem cells were allowed to differentiate to neuroepithelial cells for six days in the presence or absence of toxicants. Then, both transcriptome changes were measured (standard STOP-tox(UKN)), and cells were allowed to form rosettes. After optimization of staining methods, an imaging algorithm for rosette quantification was implemented and used for an automated rosette formation assay (RoFA). Neural tube toxicants (like valproic acid), which are known to disturb human development at stages when rosette-forming cells are present, were used as positive controls. Established toxicants led to distinctly different tissue organization and differentiation stages. RoFA outcome and transcript changes largely correlated concerning (i) the concentration-dependence, (ii) the time-dependence, and (iii) the set of positive hits identified amongst 24 potential toxicants. Using such comparative data, a prediction model for the RoFA was developed. The comparative analysis was also used to identify gene dysregulations that are particularly predictive for disturbed rosette formation. This ‘RoFA predictor gene set’ may be used for a simplified and less costly setup of the STOP-tox(UKN) assay.
Publication Title
Development of a neural rosette formation assay (RoFA) to identify neurodevelopmental toxicants and to characterize their transcriptome disturbances.
Sample Metadata Fields
Sex, Specimen part, Cell line, Treatment
View Samples- Homo sapiens
- 23 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
BACKGROUND:
Publication Title
Clinical, radiographic, and biochemical characterization of multiple myeloma patients with osteonecrosis of the jaw.
Sample Metadata Fields
No sample metadata fields
View Samples- Rattus norvegicus
- 47 Downloadable Samples
- Affymetrix Rat Gene 2.1 ST Array (ragene21st)
Description
We used old (~96-102 weeks of age) and young (~28-34 weeks of age) rats from HCR and LCR generations 29 and 32, respectively. The study included eight groups; HCR-Old-Exhausted (H-O-E, n=6), HCR-Old-Rest (H-O-R, n=6), HCR-Young-Exhausted (H-Y-E, n=6), HCR- Young -Rest (H-Y-R, n=6), LCR-Old-Exhausted (L-O-E, n=6), LCR-Old-Rest (L-O-R, n=6), LCR-Young-Exhausted (L-Y-E, n=6), and LCR- Young -Rest (L-Y-R, n=6). For the exhausted rats, dissections were performed within 10 min after the maximal running distance was reached.
Publication Title
Selection-, age-, and exercise-dependence of skeletal muscle gene expression patterns in a rat model of metabolic fitness.
Sample Metadata Fields
Specimen part
View Samples