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SRP017013
Danio rerio
3 Downloadable Samples
IlluminaHiSeq2000
Description
Human oncogenes involved in the development of hematological malignancies have been widely used to model experimental leukemia. Here, we used the fli1 promoter in zebrafish to target the expression of oncogenic HRAS to endothelial cells, including the hemogenic endothelium and observed the development of a myelo-erythroid proliferative disease. In larvae, the pathological phenotype is characterized by some disruption of the vascular system with prominent expansion of the caudal hematopoietic tissue, increase of expression of stem cell markers and myelo-erythroid specific genes and production of a large number of l-plastin leukocytes. In mosaic juveniles, increased number of hematopoietic blasts and arrest of myeloid maturation was found in kidney marrow. Peripheral blood showed delays of erythrocyte maturation and increased number of circulating myeloid progenitors. We found that the abnormal phenotype is associated with a down regulation of the Notch pathway as shown by the decrease of expression of Notch target genes, whereas overexpressing an activated form of Notch together with the oncogene prevents the expansion of the myelo-erythroid compartment. This study identifies the downregulation of the Notch pathway following an oncogenic event in the hemogenic endothelium as an important step in the pathogenesis of myelo-erythroid diseases and describes a number of potential effectors of this transformation. Overall design: Methods: mRNA profiles of transgenic zebrafish overexpressing the oncogene HRAS in endothelial cells (Tg(fli1ep:GAL4FF)ubs3; Tg(UAS:eGFP-HRASV12)io006); or expressing activate Notch in endothelial cells (Tg(fli1ep:GAL4FF)ubs3; tg(UAS:NICD)kca3) were generated by deep sequencing using Illumina HiSeq 2000. The sequence reads that passed quality filters were analyzed using the CLC bio Assembly Cell software (version 3.2) and the Ensembl (release 63) predicted cDNAs for the Zv9 genome assembly. qRT–PCR validation was performed using TaqMan and SYBR Green assays.
Publication Title
Targeting oncogene expression to endothelial cells induces proliferation of the myelo-erythroid lineage by repressing the Notch pathway.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 3 Downloadable Samples
Affymetrix Mouse Gene 1.0 ST Array (mogene10st), Affymetrix Mouse Promoter 1.0R Array (mmprompr)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
The activity-dependent histone variant H2BE modulates the life span of olfactory neurons.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Mus musculus
- 3 Downloadable Samples
- Affymetrix Mouse Promoter 1.0R Array (mmprompr), Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
We have identified a replication-independent histone variant, Hist2h2be (referred to herein as H2be), which is expressed exclusively by olfactory chemosensory neurons. Levels of H2BE are heterogeneous among olfactory neurons, but stereotyped according to the identity of the co-expressed olfactory receptor (OR). Gain- and loss-of-function experiments demonstrate that changes in H2be expression affect olfactory function and OR representation in the adult olfactory epithelium. We show that H2BE expression is reduced by sensory activity and that it promotes neuronal cell death, such that inactive olfactory neurons display higher levels of the variant and shorter life spans. Post-translational modifications (PTMs) of H2BE differ from those of the canonical H2B, consistent with a role for H2BE in altering transcription. We propose a physiological function for H2be in modulating olfactory neuron population dynamics to adapt the OR repertoire to the environment.
Publication Title
The activity-dependent histone variant H2BE modulates the life span of olfactory neurons.
Sample Metadata Fields
Age, Specimen part
View Samples- Escherichia coli
- 12 Downloadable Samples
- Affymetrix E. coli Genome 2.0 Array (ecoli2)
Description
We measured transcriptional changes in four strains P2, rpoD3, rpoA14, and rpoA27 - in an effort to understand mechanisms by which L-tyrosine production is positively influenced by the presence of mutant rpoA- and rpoD-encoded transcriptional components.
Publication Title
Rational, combinatorial, and genomic approaches for engineering L-tyrosine production in Escherichia coli.
Sample Metadata Fields
No sample metadata fields
View Samples- Saccharomyces cerevisiae
- 6 Downloadable Samples
- Affymetrix Yeast Genome 2.0 Array (yeast2)
Description
the nuclear pore complex (NPC) is emerging as an important mediator of cellular processes beyond molecule transport, including control of gene expression, replication and DNA repair.
Publication Title
The Nup84 complex coordinates the DNA damage response to warrant genome integrity.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 18 Downloadable Samples
- Illumina HiSeq 2500
Description
The recent identification of novel progenitor populations that contribute to the developing heart in a distinct temporal and spatial manner has fundamentally improved our understanding of cardiac development. However, little remains known about cardiac specification events prior to the establishment of the heart tube, or the mechanisms that direct atrial versus ventricular specification. We have identified a novel progenitor population that gives rise specifically to cardiovascular cells of the ventricles but not the atria, and to the epicardium of the differentiated heart. We determined that this cell population is first specified during gastrulation, when it transiently expresses Foxa2, a gene not previously implicated in cardiac development. Using chimeric mosaic analysis we further demonstrate that Foxa2 is cell-autonomously required for the development of ventricular cells. Finally, we reveal the existence of an analogous Foxa2+ cardiac mesoderm population during in vitro differentiation from embryonic stem cells and illustrate that these cells express genes relevant for heart development. Our data thus describe the first progenitor population identified as early as gastrulation that displays ventricular-specific differentiation potential. Together, these findings provide important new insights into the developmental origin of ventricular and atrial myocytes, and will lead to the establishment of new strategies for generating these cell types from pluripotent stem cells. Overall design: Examination of global gene expression in four different cell types
Publication Title
Foxa2 identifies a cardiac progenitor population with ventricular differentiation potential.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 6 Downloadable Samples
- IlluminaHiSeq1000
Description
Human SH-SY5Y neuroblastoma cells are widely utilized in in vitro studies to dissect out pathogenetic mechanisms of neurodegenerative disorders. These cells are considered as neuronal precursors and differentiate into more mature neuronal phenotypes under selected growth conditions. In this study, we performed systematic transcriptomic (RNA-seq) and bioinformatic analysis to pinpoint pathways and cellular processes underlying neuronal differentiation of SH-SY5Y cells according to a two-step paradigm: retinoic acid treatment followed by enriched neurobasal medium. Categorization of 1989 differentially expressed genes (DEGs) identified in differentiated cells outlined meaningful biological functions associated with changes in cell morphology including remodelling of plasma membrane and cytoskeleton, neuritogenesis. Seventy-three DEGs were assigned to Axonal Guidance Signalling pathway, and the expression of selected gene products such as neurotrophin receptors, the functionally related SLITRK6, and semaphorins, was validated by immunoblotting. Along with these findings, the differentiated cells exhibited the ability to elongate longer axonal process as assessed by the morphometric evaluation. Recognition of molecular events occurring in differentiated SH-SY5Y cells is necessary to accurately interpret the cellular responses to specific stimuli in studies on disease pathogenesis. Overall design: Comparison of cell line SH-SY5Y differentiated and undifferentiated.
Publication Title
Transcriptomic Profiling Discloses Molecular and Cellular Events Related to Neuronal Differentiation in SH-SY5Y Neuroblastoma Cells.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 51 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
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.
Publication Title
Reversible, interrelated mRNA and miRNA expression patterns in the transcriptome of Rasless fibroblasts: functional and mechanistic implications.
Sample Metadata Fields
Specimen part, Cell line, Treatment
View Samples- Saccharomyces cerevisiae
- 15 Downloadable Samples
- Affymetrix Yeast Genome 2.0 Array (yeast2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
A genome-wide function of THSC/TREX-2 at active genes prevents transcription-replication collisions.
Sample Metadata Fields
No sample metadata fields
View Samples- Saccharomyces cerevisiae
- 15 Downloadable Samples
- Affymetrix Yeast Genome 2.0 Array (yeast2)
Description
Transcription is a major obstacle for replication fork progression and a cause of genome instability. Such instability increases in mutants with a suboptimal assembly of the nascent messenger ribonucleo-protein particle (mRNP), as THO/TREX and the NPC-associated THSC/TREX-2 complex.
Publication Title
A genome-wide function of THSC/TREX-2 at active genes prevents transcription-replication collisions.
Sample Metadata Fields
No sample metadata fields
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