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GSE68169
Mus musculus
24 Downloadable Samples
Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
A detailed knowledge of the mechanisms underlying brain aging is fundamental to understand its functional decline and the baseline upon which brain pathologies superimpose. Endogenous protective mechanisms must contribute to the adaptability and plasticity still present in the healthy aged brain. Apolipoprotein D (ApoD) is one of the few genes with a consistent and evolutionarily conserved up-regulation in the aged brain. ApoD protecting roles upon stress or injury are well known, but a study of the effects of ApoD expression in the normal aging process is still missing. Using an ApoD-knockout mouse we analyze the effects of ApoD on factors contributing to the functional maintenance of the aged brain. We focused our cellular and molecular analyses in cortex and hippocampus at an age representing the onset of senescence where mortality risks are below 25%, avoiding bias towards long-lived animals. Lack of ApoD causes a prematurely aged brain without altering lifespan. Age-dependent hyperkinesia and memory deficits are accompanied by differential molecular effects in cortex and hippocampus. Transcriptome analyses reveal distinct effects of ApoD loss on the molecular age-dependent patterns of cortex and hippocampus, with different cell-type contributions to age-regulated gene expression. Markers of glial reactivity, proteostasis, and oxidative and inflammatory damage reveal early signs of aging and enhanced brain deterioration in the ApoD-knockout brain. The lack of ApoD results in an age-enhanced significant reduction in neuronal calcium-dependent functionality markers and signs of early reduction of neuronal numbers in the cortex, thus impinging upon parameters clearly differentiating neurodegenerative conditions from healthy brain aging. Our data support the hypothesis that the physiological increased brain expression of ApoD represents a homeostatic anti-aging mechanism.
Publication Title
Aging without Apolipoprotein D: Molecular and cellular modifications in the hippocampus and cortex.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Homo sapiens
- 10 Downloadable Samples
Illumina HiSeq 2000
Description
Changes in gene expression caused by CREBBP/EP300 bromodomain inhibitors in a CML cell line Overall design: K562 cells were treated with CBP30 and I-CBP112 and changes in gene expression were evaluated by RNA-seq
Publication Title
CREBBP/EP300 bromodomains are critical to sustain the GATA1/MYC regulatory axis in proliferation.
Sample Metadata Fields
Cell line, Treatment, Subject
View Samples SRP068961- Homo sapiens
- 8 Downloadable Samples
- IlluminaHiSeq2000
Description
Antiprolifereative effects of CREBBP/EP300 inhibitors were tested in human leukemia and lymphoma cell lines and the molecular mechanisms responsible for such effects were explored. Overall design: K562 cells were treated with CBP-30 (CREBBP/EP300 bromodomain inhibitor), C646 (CREBBP/EP300 HAT activity inhibitor) and JQ1 (BRD4 inhibitor) and changes in gene expression were evaluated by RNA-seq.
Publication Title
CREBBP/EP300 bromodomains are critical to sustain the GATA1/MYC regulatory axis in proliferation.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 24 Downloadable Samples
- Affymetrix Mouse Gene 2.0 ST Array (mogene20st)
Description
Considering the numerous complex and different pathological mechanisms involved in Alzheimers disease (AD) progression, treatments targeting a single cause may lead to limited benefits. The goal of this study was the identification of a novel mode of action for this unmet need. Pharmacological tool compounds: suberoylanilide hydroxamic acid (SAHA) and tadalafil, targeting histone deacetylases (HDAC) and phosphodiesterase 5 (PDE5) respectively, were utilized simultaneously for in-vitro and in-vivo Proof-of-Concept (PoC). A synergistic effect was observed in the amelioration of AD signs using the combination therapy in Tg2576 mice. Finally, a therapeutic agent, CM-414, inhibiting simultaneously HDAC2/6 and PDE5 was generated and tested in Tg2576 mice. CM-414 reversed cognitive impairment, reduced amyloid and tau pathology, and rescued dendritic spine density loss in the hippocampus in AD mice. Importantly, the effect obtained was present after a 4-weeks wash-out period.
Publication Title
Concomitant histone deacetylase and phosphodiesterase 5 inhibition synergistically prevents the disruption in synaptic plasticity and it reverses cognitive impairment in a mouse model of Alzheimer's disease.
Sample Metadata Fields
Specimen part
View Samples- Danio rerio
- 20 Downloadable Samples
- IlluminaHiSeq2000
Description
Subclassification of lymphoid neoplasms is often based on the presumed cell of origin based on T and B progenitor gene expression and the effect of cell lineage on influencing functional characteristics such as aggression and self-renewal capacity is largely unknown, accounted for in part, by lack of experimental models to address these questions. Here, we have used transgenic zebrafish to create the first models of Myc-induced B-ALL and mixed phenotypic B/T-ALL, opening new avenues for studying the these leukemias in the zebrafish. Our work has utilized syngeneic strain zebrafish, limiting dilution cell transplantation, and the widely reported rag2-Myc transgenic model to provide new understanding of how strain differences can underlie leukemia onset in the zebrafish model. Even more importantly, our work now for the first time, has allowed assessment of cell lineage on dictating aggression and leukemia stem cell frequency independent of the underlying oncogenic driver. In total, our work uncoveres that T-ALLs are more aggressive and have higher numbers of leukemia stem cells when compared with B-ALL and mixed phenotypic ALL. Furthermore, analysis of our biphenotypic B/T-ALL suggests that B cell pathways lock cells in less aggressive and lower stem cell fates and are dominant in regulating these processes when T cell pathways are co-regulated within ALL cells. Overall design: The goal of our study is to determine the transcriptional profiles of high and low self-renewing capacity tumors. 20 samples total: 11 unique samples (9 samples with biological replicates), 6 high self-renewing tumors (>1% cells could initiate leukemia) and 5 low self-renewing tumors (<1% of cells could initiate leukemia).
Publication Title
Cell of origin dictates aggression and stem cell number in acute lymphoblastic leukemia.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 37 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The objective is to generate a robust and validated predictor profile for chemotherapy response in patients with mCRC using microarray gene expression profiles of primary colorectal cancer tissue.
Publication Title
Gene expression profile predictive of response to chemotherapy in metastatic colorectal cancer.
Sample Metadata Fields
Disease, Disease stage
View Samples- Mus musculus
- 7 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Nuclear Protein 1 (Nupr1) is a major actor of the cell stress response required for KrasG12D-driven formation of pancreatic intraepithelial neoplastic (PanINs) lesions in mice. We investigated the impact of Nupr1-depletion on the development and biology of murin pancreatic adenocarcinomas (PDAC) in the Pdx1-cre;LSL-KrasG12D;Ink4a/Arffl/fl (KIC) mice. We found that only one half of Nupr1-deficient mice developed PDAC. This is related to increased caspase 3 activity and low IER3 expression in Nupr1-deficient;KIC in the pancreas. Moreover, when Nupr1-deficient;KIC mice do develop PDAC, tumors present with impaired epithelial-to-mesenchymal transition (EMT). Transcriptoma analysis revealed that Nupr1-deficient and Nupr1wt;KIC PDACs presented enrichment of gene signatures of the human classical- and quasi-mesenchymal (QM)-PDAC respectively. Moreover, Nupr1-deficient;KIC PDACs shared with human classical-PDACs overexpression of Kras-activation genes. In addition, cells derived from Nupr1-deficient;KIC PDACs formed fewer microspheres in vitro compared to Nupr1wt;KIC cells, indicative of stemness impairment in the absence of Nupr1. Finally, we found that Nupr1-deficient;KIC cells were more sensitive to some anticancer drugs than their Nupr1wt counterpart. Hence, this study establishes the pivotal role of Nupr1 in PDAC progression after PanIN and in PDAC EMT in vivo, with an impact in PDAC cell stemness. As a consequence, according to absence or presence of Nupr1, KIC mice develop tumors that phenocopy human classical- or QM-PDAC, respectively, thus becoming attractive models for preclinical drug trials.
Publication Title
Genetic inactivation of Nupr1 acts as a dominant suppressor event in a two-hit model of pancreatic carcinogenesis.
Sample Metadata Fields
Specimen part
View Samples GSE20595- Homo sapiens
- 24 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Current expression profiling methods use RNA from hundreds of thousands or thousands cells. Many fields of biology can not use microarrays due to the nature of the biological systems used that are formed by hundreds or dozens of cells. Here we present a method that can handle RNA amount limitation and gives gene expression profiles from as little as 10 cells. We first validate the method hybridizing amplified RNA from MAQC samples A and B. To do that, 25 ng or 100 pg were used and expression profiles obtained as good as when compared to Affymetrix's chemistry for amplification and labeling. The same experiment was done but using sorted cells from two comercial cell lines (SW620 and SW480) obtaining the same differential expression profiling from 2000 cells or 10 cells. The central step of the method is Whole Transcriptome Amplification (WTA) from Sigma that allows the amplification of very small amounts of RNA as starting material.
Publication Title
Accurate expression profiling of very small cell populations.
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 4 Downloadable Samples
- IlluminaHiSeq2000
Description
Gene fusions and chimeric transcripts occur frequently in cancers and in some cases drive the development of the disease. An accurate detection of these events is crucial for cancer research and in a long-term perspective could be applied for personalized therapy. RNA-seq technology has been established as an efficient approach to investigate transcriptomes and search for gene fusions and chimeric transcripts on a genome-wide scale. A number of computational methods for the detection of gene fusions from RNA-seq data have been developed. However, recent studies demonstrate differences between commonly used approaches in terms of specificity and sensitivity. Moreover their ability to detect gene fusions on the isoform level has not been studied carefully so far. Here we propose a novel computational approach called InFusion for fusion gene detection from deep RNA sequencing data. Validation of InFusion on simulated and on several public RNA-seq datasets demonstrated better detection accuracy compared to other tools. We also performed deep RNA sequencing of two well-established prostate cancer cell lines. Using these data we showed that InFusion is capable of discovering alternatively spliced gene fusion isoforms as well as chimeric transcripts that include non-exonic regions. In addition our method can detect anti-sense transcription in the fusions by incorporating strand specificity of the sequencing library. Overall design: Detection of fusion genes and chimeric transcripts from deep RNA-seq data
Publication Title
InFusion: Advancing Discovery of Fusion Genes and Chimeric Transcripts from Deep RNA-Sequencing Data.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 12 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Gene expression from MCF7 breast cancer cells at different times of TNFa incubation:pcs2 and 14-3-3 transduced cells
Publication Title
Inhibition of specific NF-κB activity contributes to the tumor suppressor function of 14-3-3σ in breast cancer.
Sample Metadata Fields
Time
View Samples