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SRP118319
Danio rerio
3 Downloadable Samples
NextSeq 500
Description
Development of specialized cell types and structures in the vertebrate heart is regulated by spatially-restricted molecular pathways. Disruptions in these pathways can cause severe congenital cardiac malformations or functional defects. To better understand these pathways and how they regulate cardiac development and function we used tomo-seq, combining high-throughput RNA sequencing with tissue sectioning, to establish a genome-wide expression dataset with high spatial resolution for the developing zebrafish heart. Analysis of the dataset revealed over 1100 genes differentially expressed in sub-compartments. Pacemaker cells in the sinoatrial region induce heart contractions, but little is known about the mechanisms underlying their development and function. Using our transcriptome map, we identified spatially restricted Wnt/ß-catenin signaling activity in pacemaker cells, which was controlled by Islet-1 activity. Moreover, Wnt/ß-catenin signaling at a specific developmental stage in the myocardium controls heart rate by regulating pacemaker cellular response to parasympathetic stimuli. Thus, this high-resolution transcriptome map incorporating all cell types in the embryonic heart can expose spatially-restricted molecular pathways critical for specific cardiac functions. Overall design: To generate spatially-resolved RNA-seq data for the developing zebrafish hearts (2 days post fertilization), we cryosectioned 3 hearts, extracted RNA from the individual sections, amplified and barcoded mRNA using the CEL-seq protocol (Hashimshony et al., Cell Reports, 2012) with a few modifications. Libraries were sequenced on Illumina NextSeq using 75bp paired end sequencing. Sample Heart #1 is the primary sample. Heart #2 and #3 are biological replicates used for comparison.
Publication Title
Spatially resolved RNA-sequencing of the embryonic heart identifies a role for Wnt/β-catenin signaling in autonomic control of heart rate.
Sample Metadata Fields
Specimen part, Subject
View Samples- Mus musculus
- 15 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
A mouse model for human small cell lung carcinoma (SCLC) has been developed based on evidence in human tumors that the tumor suppressor functions of RB and p53 are defective in more than 90% of SCLC cases. We also developed another mouse model also combines loss of p130 (Rbl2), an RB-related gene, with deletion of RB and p53. These two mouse tumors were shown to closely resemble human SCLC.
Publication Title
Loss of p130 accelerates tumor development in a mouse model for human small-cell lung carcinoma.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 17 Downloadable Samples
- Illumina HiSeq 2000
Description
We sequenced mRNA from three age groups (3months (3M), 24 months (24M) and 29 months (29M)) from the full hippocampus Overall design: There were two independent experiments: 3M vs 24M (n=5 to 6, single-end sequencing) and 3M vs 29M (n=3, paired-end sequencing))
Publication Title
De-regulation of gene expression and alternative splicing affects distinct cellular pathways in the aging hippocampus.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 52 Downloadable Samples
- IlluminaHiScanSQ
Description
UDP-sugars were identified as extracellular signaling molecules, assigning a new function to these compounds in addition to their well defined role in intracellular substrate metabolism and storage. Previously regarded as an orphan receptor, the G protein-coupled receptor (GPCR) P2Y14 (GPR105) was found to bind extracellular UDP and UDP-sugars. Little is known about the physiological functions of this GPCR. To study its physiological role we used a gene-deficient (KO) mouse strain expressing the bacterial LacZ reporter gene to monitor the physiological expression pattern of P2Y14. We found that P2Y14 is mainly expressed in pancreas and salivary glands and in subpopulations of smooth muscle cells of the gastrointestinal tract, blood vessels, lung and uterus. Among other phenotypical differences KO mice showed a significantly impaired glucose tolerance following oral and intraperitoneal glucose application. An unchanged insulin tolerance suggested altered pancreatic islet function. Transcriptome analysis of pancreatic islets showed that P2Y14 deficiency significantly changed expression of components involved in insulin secretion. Insulin secretion tests revealed a reduced insulin release from P2Y14-deficient islets highlighting P2Y14 as a new modulator of proper insulin secretion. Overall design: 10 samples from pancreatic islets isolated from wildtype mice; 10 samples from pancreatic islets isolated from P2Y14-knockout mice
Publication Title
The G protein-coupled receptor P2Y14 influences insulin release and smooth muscle function in mice.
Sample Metadata Fields
No sample metadata fields
View Samples- Drosophila melanogaster
- 11 Downloadable Samples
- Illumina HiSeq 2000, Illumina HiSeq 2500
Description
We report the application of ultrashort metabolic labeling of RNA for high-throughput profiling of RNA processing in Drosophila S2 cells. Overall design: Examination of 3 different labeling timepoints in Drosophila S2 cells.
Publication Title
The kinetics of pre-mRNA splicing in the <i>Drosophila</i> genome and the influence of gene architecture.
Sample Metadata Fields
Cell line, Subject
View Samples- Mus musculus
- 6 Downloadable Samples
- Illumina Genome Analyzer IIx, Illumina HiSeq 2000
Description
We report liver transcript profiling by RNA sequencing of Atp7b-/- and wild type mice at six weeks of age. Transcriptional network analysis of RNA-seq data reveals a highly interconnected network of transcriptional activators with over-representation of zinc-dependent and zinc-responsive transcription factors. Overall design: Wild type and Atp7b-/- Mice were maintained on strain C57BL x 129S6/SvEv. Housing was in shoebox cages and fed Mazuri Rodent diet (PMI Nutrition, Inc., Richmond, Indiana), containing 16 ppm Cu, 100 ppm Zn, and 235 ppm Fe and water ad libitum, with a 12-hour light/dark cycle. Six-week-old mice of both sexes were used for transcriptomic studies. Animals were sacrificed by carbon dioxide asphyxiation and liver tissue was harvested for RNA isolation. RNA sequencing was performed at the National Center for Genome Resources (NCGR) using the GAIIx platform. Average read quality was 38. An initial dataset was generated using two wild type and two Atp7b-/- samples with singleton 1x54 runs with 15,823,058; 8,149,631; 22,931,967 and 9,538,147 reads. A second paired end (2x54) dataset was generated to augment the initial singleton dataset with one wild type and one Atp7b-/- run resulting in 36,360,686 and 38,366,743 reads, respectively.
Publication Title
Altered zinc balance in the Atp7b<sup>-/-</sup> mouse reveals a mechanism of copper toxicity in Wilson disease.
Sample Metadata Fields
Sex, Specimen part, Cell line, Subject
View Samples- Homo sapiens
- 2 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Knockdown of HCLS1 mRNA in CD34+ hematopoietic cells resulted in a severe diminished in vitro myeloid differentiation which was in line with downregulation of a set of genes, e.g., of Wnt or PI3K/Akt signaling cascades. We performed microarrays to evaluate specific genes and signaling systems regulated by HCLS1 in hematopoietic cells.
Publication Title
Interactions among HCLS1, HAX1 and LEF-1 proteins are essential for G-CSF-triggered granulopoiesis.
Sample Metadata Fields
Specimen part, Disease, Disease stage, Treatment
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Expression 430A Array (moe430a)
Description
Wilson disease (WD) is a severe metabolic disorder caused by genetic inactivation of copper-transporting ATPase ATP7B. In WD, copper accumulates in several tissues, particularly in the liver, inducing marked time-dependent pathological changes. To identify initial events in the copper-dependent development of liver pathology we utilized the Atp7b-/- mice, an animal model for WD. Analysis of mRNA from livers of control and Atp7b-/- 6 weeks-old mice using oligonucleotide arrays revealed specific changes of the transcriptome at this stage of copper accumulation. Few messages (29 up-regulated and 46 down-regulated) change their abundance more than 2-fold pointing to the specific effect of copper on gene expression/mRNA stability. The gene ontology analysis revealed copper effects on distinct metabolic pathways.
Publication Title
High copper selectively alters lipid metabolism and cell cycle machinery in the mouse model of Wilson disease.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 43 Downloadable Samples
- Illumina HiSeq 2500
Description
Systemic sclerosis (SSc) is a devastating disease affecting the skin and internal organs. Dermal fibrosis manifests early and Modified Rodnan Skin Scores (MRSS) correlate with disease progression. Transcriptomics of SSc skin biopsies suggest the role of the in vivo microenvironment in maintaining the pathological myofibroblasts. Therefore, defining the structural changes in dermal collagen in SSc patients could inform our understanding of fibrosis pathogenesis. Here, we report a method for quantitative whole-slide image analysis of dermal collagen from SSc patients, and our findings of more aligned dermal collagen bundles in diffuse cutaneous SSc (dcSSc) patients. Using the bleomycin-induced mouse model of SSc, we identified a distinct high dermal collagen bundle alignment gene signature, characterized by a concerted upregulation in cell migration, adhesion, and guidance pathways, and downregulation of spindle, replication, and cytokinesis pathways. Furthermore, increased bundle alignment induced a cell migration gene signature in fibroblasts in vitro, and these cells demonstrated increased directed migration on aligned ECM fibers that is dependent on expression of Arhgdib (Rho GDP-dissociation inhibitor 2). Our results indicate that increased cell migration is a cellular response to the increased collagen bundle alignment featured in fibrotic skin. Moreover, many of the cell migration genes identified in our study are shared with human SSc skin and may be new targets for therapeutic intervention. Overall design: For bleomycin experiments, 8 week old C57Bl/6 female mice were used.The bleomycin model was established with daily subcutaneous injections of bleomycin (100uL at 1U/mL) into the back skin. Experimental timepoints include: saline, 2 weeks bleo, 4 weeks bleo, 6 weeks recovery, and 10 weeks recovery.
Publication Title
Increased dermal collagen bundle alignment in systemic sclerosis is associated with a cell migration signature and role of Arhgdib in directed fibroblast migration on aligned ECMs.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 15 Downloadable Samples
- Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
To obtain a genomic view of hepatocyte nuclear factor-4 (HNF-4) in the regulation of the inflammatory response, microarray analysis was used to probe the expression profile of an inflammatory response induced by cytokines in a model of knock-down HNF-4 HepG2 cells. The results indicate an extensive role for HNF-4 plays in the regulation of a large number of the liver-specific genes. Majority of genes (71%) affected by cytokine treatment are also affected by HNF-4 knock-down. This significant overlap suggests that HNF-4 may play a role in regulating the cytokine-induced inflammatory response.
Publication Title
Expression profile analysis of the inflammatory response regulated by hepatocyte nuclear factor 4α.
Sample Metadata Fields
No sample metadata fields
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