Numerous mechanisms to support cells under conditions of transient nutrient starvation have been described. The tumor suppressor protein p53 can contribute to the adaptation of cells to metabolic stress through various mechanisms that may help cancer cell survival in nutrient limiting conditions. We show here that p53 helps cancer cells to survive glutamine starvation by promoting the expression of SLC1A3, an aspartate/glutamate transporter that allows the utilization of aspartate to support cells in the absence of extracellular glutamine. Under glutamine deprivation, SLC1A3 expression maintains electron transport chain and tricarboxylic acid cycle activity, promoting de novo glutamate, glutamine and nucleotide synthesis to rescue cell viability. Tumor cells with high levels of SLC1A3 expression are resistant to glutamine starvation and SLC1A3 depletion retards the growth of these cells in vitro and in vivo, suggesting a therapeutic potential for SLC1A3 inhibition. Overall design: We quantify transcription via high throughput RNA sequencing in HCT116 cells (WT1 and WT2 clones) grown in complete medium (CM) or in glutamine-free medium (GD) for 48 hours.
A Role for p53 in the Adaptation to Glutamine Starvation through the Expression of SLC1A3.
Specimen part, Cell line, Subject
View SamplesPathological bone changes differ considerably between inflammatory arthritic diseases, and most studies have focused on bone erosion. Collagen Induced Arthritis (CIA) is a model for Rheumatoid Arthritis, which, in addition to bone erosion, demonstrates bone formation at the time for clinical manifestations. The objective of this study was to use the CIA model to study bone remodelling by performing a gene expression profiling time-course study on the CIA model.
Kinetics of gene expression and bone remodelling in the clinical phase of collagen-induced arthritis.
Specimen part
View SamplesIn rodents, the uterus of a mature
Fine temporal analysis of DHT transcriptional modulation of the ATM/Gadd45g signaling pathways in the mouse uterus.
No sample metadata fields
View Samples17-Estradiol (E2) is well known to be associated with uterine cancer, endometriosis, and leiomyomas. Although insulin-like growth factor I (IGF-I) has been identified as a mediator of the uterotrophic effect of E2 in several studies, this mechanism is still not well understood. In the present study, identification of the genes modulated by a physiological dose of E2, in the uterus, has been done in ovariectomized mice using Affymetrix microarrays. The E2-induced genomic profile shows that multiple genes belonging to the IGF-I pathway are affected after exposure to E2. Two phases of regulation could be identified. First, from 0 to 6 h, the expression of genes involved in the cell cycle, growth factors, protein tyrosine phosphatases, and MAPK phosphatases is quickly upregulated by E2, while IGF-I receptor and several genes of the MAPK and phosphatidylinositol 3-kinase pathways are downregulated. Later, i.e., from 6 to 24 h, transporters and peptidases/proteases are stimulated, whereas defense-related genes are differentially regulated by E2. Finally, cytoarchitectural genes are modulated later. The present data show that a physiological dose of E2 induces, within 24 h, a series of transcriptional events that promote the uterotrophic effect. Among these, the E2-mediated activation of the IGF-I pathway seems to play a pivotal role in the uterotrophic effect. Furthermore, the protein tyrosine phosphatases and MAPK phosphatases are likely to modulate the estrogenic uterotrophic action by targeting, at different steps, the IGF-I pathway.
Temporal analysis of E2 transcriptional induction of PTP and MKP and downregulation of IGF-I pathway key components in the mouse uterus.
No sample metadata fields
View SamplesUnder various pathophysiological muscle-wasting conditions like diabetes and starvation, a family of ubiquitin ligases, including MuRF1 (Muscle specific RING-Finger protein 1), are induced to target muscle proteins for degradation via ubiquitination. In an attempt to identify the in vivo targets of MuRF1 we have generated transgenic mouse lines overexpressing MuRF1 in a skeletal muscle specific fashion. MuRF1-TG lines were viable and had normal fertility. Characterization of their skeletal muscles did not reveal evidence for muscle wasting at 10 weeks of age. In this experiment we compared the skeletal muscle transcriptome of transgenic mice with wildtypes.
MuRF1-dependent regulation of systemic carbohydrate metabolism as revealed from transgenic mouse studies.
Sex, Age, Specimen part
View SamplesIn this study we applied genomic profiling to evaluate the transcriptomic differences between murine models ot atopic dermatitis.
Major differences between human atopic dermatitis and murine models, as determined by using global transcriptomic profiling.
Sex, Specimen part, Treatment
View SamplesDocuments of DNA expression of 4 human induced pluripotent stem cell (iPSC) lines from umbilical cord mesenchymal cells (UMCs) and amniotic mesenchymal cells (AMCs). We used microarrays to identify similarity between 4 iPSC cell lines and the human embryonic stem cell (ESC) line H9.
Generation of human induced pluripotent stem cells from umbilical cord matrix and amniotic membrane mesenchymal cells.
Specimen part, Cell line
View SamplesThe response of bacteria to the conditions at the site of infection is a key part of the transcriptional program that will determine the sucess of the infectious agent. To model the environment of the distal airway, we used bovine pulmonary surfactant (Survanta). P. aeruginosa transcript levels were measured in the presence or absence of Survanta in MOPS minimal medium to identify transcripts altered in response to surfactant. The most highly induced transcript in Survanta was PA5325, renamed sphA based on our findings that the gene was specifically induced by sphingosine derived from the sphingomyelin present in pulmonary surfactant. A divergently transcribed transcription factor, PA5324, was demonstrated to be critical for the sphingosine dependent induction of sphA and was therefore renamed SphR. Microarrays of the sphR mutant cells were compared to wild type to determine the likely SphR regulon.
Detection of host-derived sphingosine by Pseudomonas aeruginosa is important for survival in the murine lung.
Treatment
View SamplesDespite 20 years since its discovery, the gene responsible for Huntington’s Disease, HTT, has still not had its function or transcriptional profile completely characterized. In response to a recent report by Ruzo et al. of several novel splice forms of HTT in human embryonic stem cell lines, we have analyzed a set of mRNA sequencing datasets from post mortem human brain from Huntington’s disease, Parkinson’s disease, and neurologically normal control subjects to evaluate support for previously observed and to identify novel splice patterns. A custom analysis pipeline produced supporting evidence for some of the results reported by two previous studies of alternative isoforms as well as identifying previously unreported splice patterns. All of the alternative splice patterns were of relatively low abundance compared to the canonical splice form. Overall design: 29 Huntington''s Disease, 29 Parkinson''s Disease, and 50 Neurologically normal control samples from human post-mortem prefrontal cortex
Evidence of Extensive Alternative Splicing in Post Mortem Human Brain HTT Transcription by mRNA Sequencing.
No sample metadata fields
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Vitamin C enhances the generation of mouse and human induced pluripotent stem cells.
Specimen part, Treatment, Time
View Samples