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SRP018538
Danio rerio
6 Downloadable Samples
IlluminaGenomeAnalyzerII, IlluminaHiSeq2000
Description
The Gata4 transcription factor is essential for normal heart development, but the molecular basis for its function remain poorly understood. We profiled at the whole genome level transcript changes in cardiomyocytes when Gata4 is depleted from zebrafish embryos. Our objective was to elucidate the cardiomyocyte-specific molecular program functioning downstream of Gata4 in order to better understand the role of Gata4 in cardiac morphogenesis. Overall design: Six samples in total are deposited. Three replicate control samples and three replicate Gata4 morphant samples were analyzed.
Publication Title
Small heat shock proteins Hspb7 and Hspb12 regulate early steps of cardiac morphogenesis.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 8 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
The E-protein transcription factors E2A and HEB play important roles at several stages of hematopoiesis. However, the exact mechanism for theire action and the main targets in the LY6D negative common lymphoid progentior (CLP) compartment remains unknown. By adressing this question, we will gain important infromation regarding the early events leading to B-cell specification.
Publication Title
The transcription factors E2A and HEB act in concert to induce the expression of FOXO1 in the common lymphoid progenitor.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 10 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Oxidative stress in adipose tissue and liver has been linked to the development of obesity. NADPH oxidases (NOX) enzymes are a major source of reactive oxygen species (ROS). The current study was designed to determine if NOX2-generated ROS play a role in development of obesity and metabolic syndrome after high fat feeding. Wild type (WT) mice and mice lacking the cytosolic NOX2 activated protein p47phox (P47KO) were fed AIN-93G diets or high fat diets (HFD) containing 45% fat and 0.5% cholesterol for 13 weeks from weaning. Affymetrix array analysis revealed dramatically less expression of mRNA of genes linked to energy metabolism, adipocyte differentiation (PPAR, Runx2) and fatty acid uptake (CD36, lipoprotein lipase) in fat pads from female HFD-P47KO mice compared to HFD-WT females. These data suggest that NOX2 is an important regulator of metabolic homeostasis and that NOX2-associated ROS plays an important role in development of diet-induced obesity particularly in the female
Publication Title
Female mice lacking p47phox have altered adipose tissue gene expression and are protected against high fat-induced obesity.
Sample Metadata Fields
Sex, Specimen part, Treatment
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Recent studies have documented genome-wide binding patterns of transcriptional regulators and their associated epigenetic marks in hematopoietic cell lineages. In order to determine how epigenetic marks are established and maintained during developmental progression, we have generated long-term cultures of hematopoietic progenitors by enforcing the expression of the E-protein antagonist Id2. Hematopoietic progenitors that express Id2 are multipotent and readily differentiate upon withdrawal of Id2 expression into committed B lineage cells, thus indicating a causative role for E2A (Tcf3) in promoting the B cell fate. Genome-wide analyses revealed that a substantial fraction of lymphoid and myeloid enhancers are premarked by the poised or active enhancer mark H3K4me1 in multipotent progenitors. Thus, in hematopoietic progenitors, multilineage priming of enhancer elements precedes commitment to the lymphoid or myeloid cell lineages.
Publication Title
Multilineage priming of enhancer repertoires precedes commitment to the B and myeloid cell lineages in hematopoietic progenitors.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 8 Downloadable Samples
- IlluminaHiSeq2000
Description
Gene splicing requires three basal genetic elements; the 3’ and 5’ splice sites and the branchpoint to which the 5’ intron termini is ligated to form a closed lariat during the splicing reaction. The 5’ and 3’ splice sites that define exon boundaries have been widely identified, revealing pervasive transcription and splicing of human genes. However, the locations of the third requisite element, the branchpoint, are still largely unknown. Here we employ two complementary approaches, targeted RNA sequencing and exoribonuclease digestion, to distil sequenced reads that traverse the lariat junction and, via non-conventional alignment, locate human branchpoint nucleotides. Alignments identify 88,748 branchpoints that correspond to 20% of known introns, with 76% supported by diagnostic sequence mismatch errors. This affords a first genome-wide analysis of branchpoints, describing their distribution, selection, and the existence of a diverse array of overlapping sequence motifs with distinct usage, evolutionary histories, and co-variation with distal splicing elements. The overlap of branchpoints with noncoding human genetic variation also indicates a notable contribution to disease. This annotation and analysis incorporates branchpoints into transcriptomic research and reflects a core role for this element in the regulatory code that governs gene splicing and expression. Overall design: RNaseR validation of branchpoint nucleotides
Publication Title
Genome-wide discovery of human splicing branchpoints.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Recent studies have documented genome-wide binding patterns of transcriptional regulators and their associated epigenetic marks in hematopoietic cell lineages. In order to determine how epigenetic marks are established and maintained during developmental progression, we have generated long-term cultures of hematopoietic progenitors by enforcing the expression of the E-protein antagonist Id2. Hematopoietic progenitors that express Id2 are multipotent and readily differentiate upon withdrawal of Id2 expression into committed B lineage cells, thus indicating a causative role for E2A in promoting the B cell fate. Genome-wide analyses revealed that a substantial fraction of lymphoid and myeloid enhancers are pre-marked by H3K4me1 in multipotent progenitors. However, H3K4me1 levels at a subset of enhancers are elevated during developmental progression, resulting in evolving enhancer repertoires that we propose orchestrate the myeloid and B cell fates.
Publication Title
Multilineage priming of enhancer repertoires precedes commitment to the B and myeloid cell lineages in hematopoietic progenitors.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 3 Downloadable Samples
- Illumina HiSeq 2000
Description
Gene splicing requires three basal genetic elements; the 3’ and 5’ splice sites and the branchpoint to which the 5’ intron termini is ligated to form a closed lariat during the splicing reaction. The 5’ and 3’ splice sites that define exon boundaries have been widely identified, revealing pervasive transcription and splicing of human genes. However, the locations of the third requisite element, the branchpoint, are still largely unknown. Here we employ two complementary approaches, targeted RNA sequencing and exoribonuclease digestion, to distil sequenced reads that traverse the lariat junction and, via non-conventional alignment, locate human branchpoint nucleotides. Alignments identify 88,748 branchpoints that correspond to 20% of known introns, with 76% supported by diagnostic sequence mismatch errors. This affords a first genome-wide analysis of branchpoints, describing their distribution, selection, and the existence of a diverse array of overlapping sequence motifs with distinct usage, evolutionary histories, and co-variation with distal splicing elements. The overlap of branchpoints with noncoding human genetic variation also indicates a notable contribution to disease. This annotation and analysis incorporates branchpoints into transcriptomic research and reflects a core role for this element in the regulatory code that governs gene splicing and expression. Overall design: CaptureSeq identification of branchpoint nucleotides
Publication Title
Genome-wide discovery of human splicing branchpoints.
Sample Metadata Fields
Cell line, Subject
View Samples- Homo sapiens
- 27 Downloadable Samples
- Illumina HiSeq 1000
Description
Inhibition of mTOR signaling using the rapalog everolimus is an FDA-approved targeted therapy for patients with lung and gastroenteropancreatic neuroendocrine tumors (NET). However, patients eventually progress on treatment, highlighting the need for additional therapies. We focused on pancreatic NETs (pNETs) and reasoned that treatment of these tumors upon progression on rapalog therapy, with an mTOR kinase inhibitor (mTORKi) such as CC-223 could overcome a number of resistance mechanisms in tumors and delay cardiac carcinoid disease. We performed preclinical studies using human pNET cells in vitro and injected them subcutaneously or orthotopically to determine tumor progression and cardiac function in mice treated with either rapamycin alone or switched to CC-223 upon progression. Detailed signaling and RNA sequencing analyses were performed on tumors that were sensitive or progressed on mTOR treatment. Approximately 57% of mice bearing pNET tumors which progressed on rapalog therapy showed a significant decrease in tumor volume upon a switch to CC-223. Moreover, mice treated with an mTORKi exhibited decreased cardiac dilation and thickening of heart valves than those treated with placebo or rapamycin alone. In conclusion, in the majority of pNETs that progress on rapalogs, it is possible to reduce disease progression using an mTORKi, such as CC-223. Moreover, CC-223 had an additional transient cardiac benefit on valvular fibrosis compared to placebo- or rapalog-treated mice. These results provide the preclinical rationale to further develop mTORKi clinically upon progression on rapalog therapy and to further test their long term cardioprotective benefit in those NET patients prone to carcinoid syndrome. Overall design: We performed RNA sequencing analyses as an unbiased means to assess changes in gene expression. Our major goal was to identify the differences in tumor mRNAs between the CC-223- and non-CC-223 responders compared to the rapamycin alone treatment arm (Fig 5A in Orr-Asman et al manuscript). The analysis was conducted using 1 tumor each from 13 and 14 mice treated with rapamycin or switched to CC-223 respectively.
Publication Title
mTOR Kinase Inhibition Effectively Decreases Progression of a Subset of Neuroendocrine Tumors that Progress on Rapalog Therapy and Delays Cardiac Impairment.
Sample Metadata Fields
Specimen part, Subject
View Samples- Mus musculus
- 20 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Hematopoietic stem cells (HSC) continuously regenerate a complete hematologic and immune system. Very few genes that regulate this process have yet been identified. In order to identify factors governing differentiation, we have compared the transcriptome of highly purified HSC with their differentiated progeny, including erythrocytes, granulocytes, monocytes, NK cells, activated and nave T-cells, and B-cells. Chromosomal analysis revealed that HSC were more transcriptionally active than other cell types across most chromosomes. Each lineage expressed ~100 to 400 genes uniquely, including many previously uncharacterized genes. Overexpression of two fingerprint genes resulted in a significant bias in differentiation indicating a role in cell fate determination, demonstrating the utility of these data for modulation of specific cell types.
Publication Title
Hematopoietic fingerprints: an expression database of stem cells and their progeny.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 53 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Contractile and highly synthetic myofibroblasts are the key effector cells involved in excessive extracellular matrix (ECM) deposition in multiple fibrotic conditions, including idiopathic pulmonary fibrosis (IPF). In order to define the key drivers of the fibrotic response, we used laser capture microdissection to isolate RNA from myofibroblasts within fibroblastic foci and performed microarray analysis in combination with a novel eigengene approach to identify functional clusters of genes which associate with collagen gene expression.
Publication Title
Transcriptome analysis of IPF fibroblastic foci identifies key pathways involved in fibrogenesis.
Sample Metadata Fields
Specimen part, Disease, Subject
View Samples