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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
- 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
- 10 Downloadable Samples
- IlluminaHiSeq2500
Description
We report gene expression data for human melanoma cell lines using RNAseq. Overall design: RNAseq was performed on 8 melanoma cell lines and one normal human melanocyte cell line. All done as single replicates, except for two biological replicates of A375.
Publication Title
A zebrafish melanoma model reveals emergence of neural crest identity during melanoma initiation.
Sample Metadata Fields
No sample metadata fields
View Samples- Danio rerio
- 2 Downloadable Samples
- IlluminaHiSeq2500
Description
We report gene expression data for FACS sorted zebrafish crestin_1kb:EGFP + cells collected at 15 somite stage (SS). Overall design: crestin_1kb:EGFP + embryos were homogenized, filtered, and sorted using FACS into PBS, collecting ~5,500 EGFP (+) cells and 100K EGFP (-) cells with a single sample for each.
Publication Title
A zebrafish melanoma model reveals emergence of neural crest identity during melanoma initiation.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 24 Downloadable Samples
- IlluminaHiSeq2500
Description
Cancer metabolism has been actively studied to gain insights into tumorigenic survival mechanisms and susceptibilities. In melanoma, we identify HEXIM1, a transcription elongation regulator, as a novel melanoma suppressor that participates in nucleotide stress regulation. HEXIM1 expression is low in melanoma. Its overexpression suppresses melanoma while its inactivation accelerates tumor onset in vivo. HEXIM1 responds to nucleotide stress. Knockdown of HEXIM1 rescues neural crest and melanoma nucleotide stress phenotypes in vivo. Mechanistically, under nucleotide stress, HEXIM1 is induced to form an inhibitory complex with P-TEFb, the kinase that initiates transcription elongation, to pause transcription at tumorigenic genes. The resulting alteration in gene expression also causes anti-tumorigenic transcripts to bind to and be stabilized by HEXIM1. HEXIM1 therefore plays an important role in inhibiting cancer cell-specific gene transcription while also facilitating anti-cancer gene expression. Our study reveals a novel role for HEXIM1 in coupling nucleotide metabolism with transcriptional regulation in melanoma. Overall design: RNA-seq analysis of human A375 melanoma cells treated with either DMSO or 25 µM A771726 for 0-72 hrs.
Publication Title
Stress from Nucleotide Depletion Activates the Transcriptional Regulator HEXIM1 to Suppress Melanoma.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 12 Downloadable Samples
- IlluminaHiSeq2500
Description
Cancer metabolism has been actively studied to gain insights into tumorigenic survival mechanisms and susceptibilities. In melanoma, we identify HEXIM1, a transcription elongation regulator, as a novel melanoma suppressor that participates in nucleotide stress regulation. HEXIM1 expression is low in melanoma. Its overexpression suppresses melanoma while its inactivation accelerates tumor onset in vivo. HEXIM1 responds to nucleotide stress. Knockdown of HEXIM1 rescues neural crest and melanoma nucleotide stress phenotypes in vivo. Mechanistically, under nucleotide stress, HEXIM1 is induced to form an inhibitory complex with P-TEFb, the kinase that initiates transcription elongation, to pause transcription at tumorigenic genes. The resulting alteration in gene expression also causes anti-tumorigenic transcripts to bind to and be stabilized by HEXIM1. HEXIM1 therefore plays an important role in inhibiting cancer cell-specific gene transcription while also facilitating anti-cancer gene expression. Our study reveals a novel role for HEXIM1 in coupling nucleotide metabolism with transcriptional regulation in melanoma. Overall design: RNA-seq analysis of human Tet-On HEXIM1-inducible A375 melanoma cells treated with either DMSO or 1 µg/mL doxycycline in triplicate for 48 hrs.
Publication Title
Stress from Nucleotide Depletion Activates the Transcriptional Regulator HEXIM1 to Suppress Melanoma.
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