Analysis of the transcriptional profiles of mRNA and microRNA in Rasless fibroblasts. 4-Hydroxy-tamoxifen (4-OHT) treatment triggers removal of K-Ras expression in [H-Ras-/-;N-Ras-/-;K-Raslox/lox;RERTert/ert ] mouse fibroblasts (named K-Raslox) generating Rasless MEFs which are unable to proliferate, but recover proliferative ability after ectopic expression of constitutively active downstream kinases such as BRAF and MEK1.
Reversible, interrelated mRNA and miRNA expression patterns in the transcriptome of Rasless fibroblasts: functional and mechanistic implications.
Specimen part, Cell line, Treatment
View SamplesRNA sequencing of T-ALL tumors derived from genetically modified mouse models: CIC loss-of-function, HRASG12V driven from the Kras promoter and Trp53 KO. Results provide insight into the role of the RAS/CIC axis in T-ALL development. Overall design: RNA-Sequencing of 5 CIC LOF, 3 K:HrasG12V and 4 Trp53 KO T-ALL murine tumor samples.
Inactivation of Capicua in adult mice causes T-cell lymphoblastic lymphoma.
Cell line, Treatment, Subject
View SamplesInvestigation of the transcriptome profile of lung dendritic cells (DCs) of two genetically different pig breeds (Pietrain and Duroc) after PRRSV infection in vitro and determination of the temporal changes in transcriptional profiles. Overall design: Pietrain and Duroc lung DCs were isolated and infected in vitro with PRRSV. Total cellular mRNA from non-infected (0 hours) and infected (3, 6, 9, 12 and 24 hours post infection) lung DCs was extracted and 12 lung DCs samples were used for the global transcriptome profile analysis (RNA-Seq).
Transcriptome profile of lung dendritic cells after in vitro porcine reproductive and respiratory syndrome virus (PRRSV) infection.
Sex, Specimen part, Subject
View SamplesWe applied in parallel RNA-Seq and Ribosome-profiling analyses to immortalized human primary BJ fibroblast cells under the following conditions: normal proliferation, quiescence (induced by serum depletion), senescence (induced by activation of the oncogenic RASG12V gene, and examined at early (5 days; pre-senescent state) and late (14 days; fully senescent state) time points), and neoplastic transformation (induced by RASG12V in the background of stable p53 and p16INK4A knockdowns and SV40 small-T expression. Overall design: RNA-seq, using Illumina HiSeq 2000, was applied to BJ cells under 5 conditions: proliferation, quiescence, pre-senescence, full-senescence, and transfomed. Ribosome profiling, using Illumina HiSeq 2000, was applied to BJ cells under 5 conditions: proliferation, quiescence, pre-senescence, full-senescence, and transfomed.
p53 induces transcriptional and translational programs to suppress cell proliferation and growth.
No sample metadata fields
View SamplesWe applied in parallel RNA-Seq and Ribosome-profiling analyses to immortalized human primary BJ fibroblast cells in which p53 was induced by Nutlin-3a Overall design: RNA-seq, using Illumina HiSeq 2000, was applied to BJ cells treated with Nutlin-3a, at 5 timepoints: 0, 2, 4, 6, 19 hrs Ribosome profiling was applied to BJ cells treated with Nutlin-3a, at 5 timepoints: 0, 2, 4, 6, 19 hrs
p53 induces transcriptional and translational programs to suppress cell proliferation and growth.
No sample metadata fields
View SamplesOncogene-induced senescence (OIS) is a p53-dependent defence mechanism against uncontrolled proliferation. Consequently, many human tumours harbour p53 mutations while others show a dysfunctional p53 pathway, frequently by unknown mechanisms. We identified BRD7, a bromodomain-containing protein whose inhibition allows full neoplastic transformation in the presence of wild-type p53. Intriguingly, in human breast tumours harbouring wild-type, but not mutant p53, the BRD7 gene locus was frequently deleted and low BRD7 expression was found in a subgroup of tumours. Functionally, BRD7 is required for efficient p53-mediated transcription of a subset of target genes. BRD7 interacts with p53 and p300, and is recruited to target gene promoters, affecting histone acetylation, p53 acetylation, and promoter activity. Thus, BRD7 suppresses tumourigenicity by serving as a p53 cofactor required for efficient induction of p53-dependent OIS.
BRD7 is a candidate tumour suppressor gene required for p53 function.
Specimen part, Disease, Cell line
View SamplesWe applied deep-sequencing based technique, 3''-Seq, to obtain comprehansive maps of poly-A sites in human cells. 3''-Seq was applied to two cell lines (U2OS and RPE-1), in control and PABPN1 knockdown cells Overall design: Examination of poly-A sites in control and PABPN1kd cells (in two different cell lines)
The poly(A)-binding protein nuclear 1 suppresses alternative cleavage and polyadenylation sites.
No sample metadata fields
View SamplescJun is a transcription factor activated by phosphorylation by SAPK/JNK MAP kinase pathway that has been linked to atherosclerosis. Adenovirus mediated gene transfer of a dominant negative form of cJun in C57BL/6 mice increased greatly the apolipoprotein E (ApoE) mRNA and plasma apoE levels and induced dyslipidmia, characterized by increased plasma cholesterol, triglyceride and VLDL levels and accumulation of discoidal HDL particles. Unexpectedly, infection of ApoE-/- mice with adenovirus expressing dn-cJun reduced by 50% plasma cholesterol, suggesting that the dn-cJun affected other genes that control plamsa cholesterol. To determine the molecular pathways implicated in this process we performed whole genome expression profiling using total RNA from the liver of infected ApoE-/- mice.
A dominant negative form of the transcription factor c-Jun affects genes that have opposing effects on lipid homeostasis in mice.
No sample metadata fields
View SamplesThis series analyses germinating Arabidopsis seeds with both temporal and spatial detail, revealing two transcriptional phases that are separated with respect to testa rupture. Performed as part of the ERA-NET Plant Genomics grant vSEED.
Transcriptional dynamics of two seed compartments with opposing roles in Arabidopsis seed germination.
Specimen part, Time
View SamplesDespite its key role in Alzheimer pathogenesis, the physiological function(s) of the amyloid precursor protein (APP) and of its proteolytic fragments are still poorly understood. The secreted APPs ectodomain has been shown to be involved in neuroprotection and synaptic plasticity. The -secretase generated APP intracellular domain, AICD, functions as a transcriptional regulator in heterologous reporter assays although its role for endogenous gene regulation has remained controversial. Previously, we have generated APPs knockin (KI) mice expressing solely the secreted ectodomain APPs. Here, we generated double mutants (APPs-DM) by crossing APPs-KI mice onto an APLP2-deficient background and show that APPs rescues the postnatal lethality of the majority of APP/APLP2 double knockout mice. Despite normal CNS morphology and unaltered basal synaptic transmission, young APPs-DM mice already showed pronounced hippocampal dysfunction, impaired spatial learning and a deficit in LTP. To gain further mechanistic insight into which domains/proteolytic fragments are crucial for hippocampal APP/APLP2 mediated functions, we performed a DNA microarray transcriptome profiling of prefrontal cortex and hippocampus of adult APLP2-KO (APLP2-/-) and APPs-DM mice (APP/APLP2-/- mice).Interestingly, this analysis failed to reveal major genotype-related transcriptional differences. Expression differences between cortex and hippocampus were, however, readily detectable.
APP and APLP2 are essential at PNS and CNS synapses for transmission, spatial learning and LTP.
Sex, Specimen part
View Samples