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Drosophila melanogaster
6 Downloadable Samples
Affymetrix Drosophila Genome 2.0 Array (drosophila2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
dDsk2 regulates H2Bub1 and RNA polymerase II pausing at dHP1c complex target genes.
Sample Metadata Fields
Cell line
View Samples- Drosophila melanogaster
- 6 Downloadable Samples
- Affymetrix Drosophila Genome 2.0 Array (drosophila2)
Description
Heterochromatin-protein 1 (HP1) is a functionally diverse family of proteins. In particular, Drosophila dHP1c forms a complex with the transcription factors WOC and ROW (dHP1EU) that localizes at euchromatin and regulates gene expression.
Publication Title
dDsk2 regulates H2Bub1 and RNA polymerase II pausing at dHP1c complex target genes.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 12 Downloadable Samples
- Illumina human-6 v2.0 expression beadchip
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Reprogramming transcription by distinct classes of enhancers functionally defined by eRNA.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 12 Downloadable Samples
- Illumina human-6 v2.0 expression beadchip
Description
Mammalian genomes are populated with thousands of transcriptional enhancers that orchestrate cell type-specific gene expression programs; however, the potential that there are pre-established enhancers in different functional classes that permit alternative signal-dependent transcriptional responses has remained unexplored. Here we present evidence that cell lineage-specific factors, such as FoxA1, can simultaneously facilitate and restrict key regulated transcription factors, exemplified by the androgen receptor (AR), acting at structurally- and functionally-distinct classes of pre-established enhancers, thus licensing specific signal-activated responses while restricting others. Consequently, FoxA1 down-regulation, an unfavorable prognostic sign in advanced prostate tumors, causes a massive switch in AR binding from one functional class of enhancers to another, with a parallel switch in levels of enhancer-templated non-coding RNAs (eRNAs) revealed by the global run-on assay (GRO-seq), which documents the dramatic reprogramming of the hormonal response. The molecular basis for this switch lies in the release of FoxA1-mediated restriction of AR binding to the new enhancer class with no apparent nucleosome remodeling, which is required for stimulating their eRNA transcription and/or enhancing enhancer:promoter looping and gene activation. Together, these findings reveal a large repository of pre-determined enhancers in the human genome that can be dynamically tuned to induce their transcription and activation of alternative gene expression programs, which may underlie many sequential gene expression events in development or during disease progression.
Publication Title
Reprogramming transcription by distinct classes of enhancers functionally defined by eRNA.
Sample Metadata Fields
Specimen part
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
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- 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
- 4 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Transcription factro-EB (TFEB) is a master gene for autophagy and lysosome biogenesis
Publication Title
Endothelial TFEB (Transcription Factor EB) Positively Regulates Postischemic Angiogenesis.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 11 Downloadable Samples
- Affymetrix Human Exon 1.0 ST Array [probe set (exon) version (huex10st)
Description
In order to identify genes with different overall transcript levels or differential exon levels (alternative processing) between the groups Control and Tat-SF1KD, we studied 11 hybridizations on the HumanExon10ST array using mixed model analysis of variance. 526 genes with significant transcript level differences between the groups and 1397 genes with significant differential exon levels were found, including 99 genes with both transcript and exon level differences (p<0.01).
Publication Title
Identification of Tat-SF1 cellular targets by exon array analysis reveals dual roles in transcription and splicing.
Sample Metadata Fields
Cell line
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
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