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SRP062866
Mus musculus
8 Downloadable Samples
Illumina Genome Analyzer II
Description
Status epilepticus (SE) is a life-threatening condition that can give rise to a number of neurological disorders, including learning deficits, depression, and epilepsy. Many of the effects of SE appear to be mediated by alterations in gene expression. To gain deeper insight into how SE affects the transcriptome, we employed the pilocarpine SE model in mice and Illumina-based high-throughput sequencing to characterize alterations in gene expression from the induction of SE, to the development of spontaneous seizure activity. While some genes were upregulated over the entire course of the pathological progression, each of the three sequenced time points (12-hour, 10-days and 6-weeks post-SE) had a largely unique transcriptional profile. Hence, genes that regulate synaptic physiology and transcription were most prominently altered at 12-hours post-SE; at 10-days post-SE, marked changes in metabolic and homeostatic gene expression were detected; at 6-weeks, substantial changes in the expression of cell excitability and morphogenesis genes were detected. At the level of cell signaling, KEGG analysis revealed dynamic changes within the MAPK pathways, as well as in CREB-associated gene expression. Notably, the inducible expression of several noncoding transcripts was also detected. These findings offer potential new insights into the cellular events that shape SE-evoked pathology. Overall design: cDNA from two animals was pooled into two independent biological replicates for each timepoint (ie. two sets of two animals per experimental group: control, 12 hours, 10 days, 6 weeks). Samples were sequenced using a Genome Analyzer II (GAII) at a concentration of 10pM in each lane. Base-calling was conducted with the standard Illumina Analysis Pipeline 1.0 (Firescrest-Bustard). Eight FASTQ sequence files (sequencing reads plus quality information) were generated and mapped to the mouse genome (UCSC mm9) using the Bowtie algorithm with default settings. A C++ program was used to count the number of uniquely mapped reads within exons of Ref-Seq genes (UCSC Genome Browser mm9 annotation).
Publication Title
Status epilepticus stimulates NDEL1 expression via the CREB/CRE pathway in the adult mouse brain.
Sample Metadata Fields
Cell line, Subject, Time
View Samples- Vitis vinifera
- 8 Downloadable Samples
Affymetrix Vitis vinifera (Grape) Genome Array (vitisvinifera)
Description
Overexpression of a grapevine C-repeat binding factor (CBF) gene, VvCBF4 in cv. Freedom was found to improve freezing survival in non-cold-acclimated vines.
Publication Title
The Vitis vinifera C-repeat binding protein 4 (VvCBF4) transcriptional factor enhances freezing tolerance in wine grape.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 12 Downloadable Samples
- Illumina HiSeq 2500
Description
The p53 protein is the most frequently inactivated tumor suppressor in human cancer. While p53 mutations are found in 50% of all cancers, the p53 pathway can also be suppressed by its interaction with endogenous inhibitors HDMX and HDM2, which are frequently overexpressed in patients with acute myeloid leukemia and other cancers. Thus, pharmacological disruption of both these interactions is an attractive strategy to restore p53-dependent tumor suppressor activity in AML with wild type P53. Strategies targeting HDM2 have recently generated promising results; however, cancer cells are still left vulnerable to p53 inhibition by HDMX, particularly in cancers such as leukemia that overexpress HDMX. In this study, we demonstrate that dual HDMX/HDM2 inhibition using a stapled alpha-helical peptide (ALRN-6924), which has recently entered clinical testing, leads to striking anti-leukemic effects. ALRN-6924 robustly activates p53-dependent transcription at the single cell and single molecule level, and exhibits biochemical and molecular biological on-target activity in leukemia cells in vitro and in a patient who received ALRN-6924 treatment. Dual HDMX/HDM2 inhibition by ALRN-6924 inhibits cellular proliferation by inducing cell cycle arrest and apoptosis in cell lines and primary AML patients' cells, including in leukemic stem cell-enriched populations, and disrupts functional clonogenic and serial replating capacity. Furthermore, ALRN-6924 leads to significantly improved survival in an AML xenograft model in vivo. At the molecular level, dual HDMX/HDM2 inhibition leads to global transcriptional activation of p53-dependent pathways in leukemia cells. Our study provides insight into the effects of dual HDMX/HDM2 inhibition and proof-of-concept for ALRN-6924 as a novel therapeutic approach in AML and other cancers with high HDMX levels. Overall design: Total mRNA expression profiles of vehicle (1:10 DMSO) or 1 uM ALRN-6924 treated AML cells (6 hours) were generated by deep sequencing, in triplicates, using the Illumnia HiSeq 2500 instrument.
Publication Title
Dual inhibition of MDMX and MDM2 as a therapeutic strategy in leukemia.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Cells undergoing apoptosis are known to modulate their tissue microenvironments. By acting on phagocytes, notably macrophages, apoptotic cells inhibit immunological and inflammatory responses and promote trophic signaling pathways. Paradoxically because of their potential to cause death of tumor cells and thereby militate against malignant disease progression, both apoptosis and tumor-associated macrophages (TAM) are often associated with poor prognosis in cancer. In order to better understand the influence of tumor cell apoptosis and in particular its effect on TAM, we investigated global gene expression signatures of undisturbed TAM engaged in engulfment of apoptotic tumor cells. We studied a xenograft model of an aggressive starry-sky non-Hodgkins lymphoma, Burkitts lymphoma (BL), in which apoptotic tumor cells are common and frequently observed in association with the starry-sky TAM (SS-TAM, so called because they appear histologically as stars in a sky of tumor cells) that accumulate in these tumors. We used a BL cell line (BL2) whose cells phenotypically resemble the tumor biopsy cells from which the line was derived including the capacity to undergo apoptosis constitutively. BL xenografts in SCID mice closely recapitulated the starry-sky histological picture of the human lymphoma. Due to the high sensitivity of macrophages to their environments, we adopted laser-capture microdissection of individual SS-TAM in BL xenografts in order to obtain unbiased in situ transcriptional profiles of these cells, which we compared specifically with those of similarly-captured macrophages, the tingible-body macrophages from normal germinal centers (GCM). The rationale for this comparison was based upon BL being a germinal center malignancy and tingible-body macrophages being regarded as normal equivalents of SS-TAM.
Publication Title
Oncogenic properties of apoptotic tumor cells in aggressive B cell lymphoma.
Sample Metadata Fields
Sex, Specimen part
View Samples- Arabidopsis thaliana
- 28 Downloadable Samples
- Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)
Description
In depth temporal profiling of transcript changes at 10 time points during germination in Arabidopsis seed was carried out. The time course utilised, encompassed seed maturation, stratification, germination and post-germination and provided a global investigation into the tightly regulated, phasic changes that define seed germination.
Publication Title
In-depth temporal transcriptome profiling reveals a crucial developmental switch with roles for RNA processing and organelle metabolism that are essential for germination in Arabidopsis.
Sample Metadata Fields
Specimen part, Disease, Time
View Samples- Mus musculus
- 8 Downloadable Samples
- Affymetrix Mouse Clariom S Array (clariomsmouse)
Description
Microglia are the brain-resident myeloid cells of the parenchyma. We study the roles microglia play in response to virus infection.
Publication Title
Microglia are required for protection against lethal coronavirus encephalitis in mice.
Sample Metadata Fields
Age, Specimen part, Time
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Clariom S Array (clariomsmouse)
Description
Hematogenous macrophages infiltrate the brain after virus infection. We use a CSF1R inhibitior, PLX5622 to deplete microglia from the brain. However, macrophages also express the CSF1R and may be affected by PLX5622-treatment of mice.
Publication Title
Microglia are required for protection against lethal coronavirus encephalitis in mice.
Sample Metadata Fields
Age, Specimen part, Time
View Samples- Homo sapiens
- 24 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
Global gene experssion study of the HAEC transcriptional response to artificial chlyomicron remnant-like particles (A-CRLPs) prepared with triglycerides extracted from four natural dietary oils: fish, DHASCO, corn and palm oils. We hypothesised that A-CRLPs could differentially regulate HAEC gene expression according to thier triglyceride content. These data provide an important starting point for investigations into the effects of A-CRLPs on endothelial cells, particulary genes involved in redox balance and inflammatory processes.
Publication Title
Endothelial HO-1 induction by model TG-rich lipoproteins is regulated through a NOX4-Nrf2 pathway.
Sample Metadata Fields
Specimen part
View Samples- Oryza sativa
- 24 Downloadable Samples
- Affymetrix Rice Genome Array (rice)
Description
In response to bacterial infection, early transcriptional re-programming occurs in the host plant.
Publication Title
Antagonistic, overlapping and distinct responses to biotic stress in rice (Oryza sativa) and interactions with abiotic stress.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 10 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Epilepsy is a common cause of morbidity affecting approximately one third of patients with primary brain tumors. However, the molecular mechanism underlying the tumor induced epileptogenesis is poorly understood. The alteration in peritumoral microenvironments is believed to play a significant role in inducing epileptogenesis.
Publication Title
Transcriptomic profiling of human peritumoral neocortex tissues revealed genes possibly involved in tumor-induced epilepsy.
Sample Metadata Fields
Sex, Specimen part, Disease, Disease stage
View Samples