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SRP041263
Homo sapiens
2 Downloadable Samples
IlluminaHiSeq2000
Description
Ewing sarcoma is an aggressive pediatric small round cell tumor that predominantly occurs in bone. Approximately 85% of Ewing sarcomas harbor the EWS/FLI fusion protein, which arises from a chromosomal translocation, t(11:22)(q24:q12). EWS/FLI interacts with numerous lineage-essential transcription factors to maintain mesenchymal progenitors in an undifferentiated state. We previously showed that EWS/FLI binds the osteogenic transcription factor RUNX2 and prevents osteoblast differentiation. In this study, we investigated the role of another Runt-domain protein, RUNX3, in Ewing sarcoma. RUNX3 participates in mesenchymal-derived bone formation and is a context dependent tumor suppressor and oncogene. RUNX3 was detected in all Ewing sarcoma cells examined, whereas RUNX2 was detected in only 73% of specimens. Like RUNX2, RUNX3 binds to EWS/FLI via its Runt domain. EWS/FLI prevented RUNX3 from activating the transcription of a RUNX-responsive reporter, p6OSE2. Stable suppression of RUNX3 expression in the Ewing sarcoma cell line A673 delayed colony growth in anchorage independent soft agar assays and reversed expression of EWS/FLI-responsive genes. These results demonstrate an important role for RUNX3 in Ewing sarcoma. Overall design: RNA-seq to compare transcriptiome of control A673 ewing sarcoma cells stably expression a non-target or RUNX3 shRNA
Publication Title
RUNX3 facilitates growth of Ewing sarcoma cells.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 1 Downloadable Sample
Illumina MouseRef-8 v2.0 expression beadchip
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Runx2 is required for early stages of endochondral bone formation but delays final stages of bone repair in Axin2-deficient mice.
Sample Metadata Fields
Sex
View Samples- Mus musculus
- 1 Downloadable Sample
- Illumina MouseRef-8 v2.0 expression beadchip
Description
Runx2 and Axin2 regulate skeletal development. We recently determined that Axin2 and Runx2 molecularly interact in differentiating osteoblasts to regulate intramembranous bone formation, but the relationship between these factors in endochondral bone formation was unresolved. To address this, we examined the effects of Axin2 deficiency on the cleidocranial dysplasia (CCD) phenotype of Runx2+/-mice, focusing on skeletal defects attributed to improper endochondral bone formation. Axin2 deficiency unexpectedly exacerbated calvarial components of the CCD phenotype in the Runx2+/-mice; the endocranial layer of the frontal suture, which develops by endochondral bone formation, failed to mineralize in the Axin2-/-:Runx2+/-mice, resulting in a cartilaginous, fibrotic and larger fontanel than observed in Runx2+/-mice. Transcripts associated with cartilage development (e.g., Acan, miR140) were expressed at higher levels, whereas blood vessel morphogenesis transcripts (e.g., Slit2) were suppressed in Axin2-/-:Runx2+/-calvaria. Cartilage maturation was impaired, as primary chondrocytes from double mutant mice demonstrated delayed differentiation and produced less calcified matrix in vitro. The genetic dominance of Runx2 was also reflected during endochondral fracture repair, as both Runx2+/-and double mutant Axin2-/-:Runx2+/-mice had enlarged fracture calluses at early stages of healing. However, by the end stages of fracture healing, double mutant animals diverged from the Runx2+/-mice, showing smaller calluses and increased torsional strength indicative of more rapid end stage bone formation as seen in the Axin2-/-mice. Taken together, our data demonstrate a dominant role for Runx2 in chondrocyte maturation, but implicate Axin2 as an important modulator of the terminal stages of endochondral bone formation.
Publication Title
Runx2 is required for early stages of endochondral bone formation but delays final stages of bone repair in Axin2-deficient mice.
Sample Metadata Fields
Sex
View Samples- Mus musculus
- 2 Downloadable Samples
- Illumina HiSeq 2000
Description
Histone deacetylase inhibitors are efficacious epigenetic-based therapies for some cancers and neurological disorders; however, these drugs inhibit multiple Hdacs and have detrimental effects on the pre- and post-natal skeleton. To better understand how Hdac inhibitors affect the skeleton, we focused on understanding the role of one of their targets, Hdac3, in endochondral bone formation by deleting it in immature murine chondrocyte micro masses with Adeno-Cre. Hdac3-deficient chondrocytes expressed higher levels of pro-inflammatory and matrix degrading genes (e.g., Il-6, Mmp3, Mmp13, Saa3) and lower levels of genes related to the extracellular matrix production, bone development and ossification (e.g., Acan, Col2a1, Ihh, Col10a1). Histone acetylation was increased in and around genes with elevated expression. Overall design: High Throughput RNA sequencing and Chromatin immunopreciptation sequencing experiments were performed in chondrocyte cultures. Differential analysis was conducted on ChIP-seq and RNA-seq data to identify H3K27Ac profile for up and down regulated genes in Hdac3-deficient murine chondrocytes.
Publication Title
Histone deacetylase 3 supports endochondral bone formation by controlling cytokine signaling and matrix remodeling.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Bos taurus
- 47 Downloadable Samples
- Illumina Genome Analyzer II
Description
Background: Weaning of beef calves is a necessary husbandry practice and involves separating the calf from its mother, resulting in numerous stressful events including dietary change, social reorganisation and the cessation of the maternal-offspring bond and is often accompanied by housing. While much recent research has focused on the physiological response of the bovine immune system to stress in recent years, little is known about the molecular mechanisms modulating the immune response. Therefore, the objective of this study was to provide new insights into the molecular mechanisms underlying the physiological response to weaning at housing in beef calves using Illumina RNA-seq. Results: The leukocyte transcriptome was significantly altered for at least 7 days following either housing or weaning at housing. Analysis of differentially expressed genes revealed that four main pathways, cytokine signalling, transmembrane transport, haemostasis and G-protein-coupled receptor (GPRC) signalling, were differentially regulated between control and weaned calves and underwent significant transcriptomic alterations in response to weaning stress on day 1, 2 and 7. Of particular note, chemokines, cytokines and integrins were consistently found to be up-regulated on each day following weaning. Evidence for alternative splicing of genes was also detected, indicating that a number of genes involved in the innate and adaptive immune response may be alternatively transcribed, including those responsible for toll receptor cascades and T cell receptor signalling. Conclusions: This study represents the first application of RNA-Seq technology for genomic studies in bovine leukocytes in response to weaning stress. Weaning stress induces the activation of a number of cytokine, chemokine and integrin transcripts and may alter the immune system whereby the ability of a number of cells of the innate and adaptive immune system to locate and destroy pathogens is transcriptionally enhanced. Stress alters the homeostasis of the transcriptomic environment of leukocytes for at least 7 days following weaning, indicating long-term effects of stress exposure in the bovine. The identification of gene signature networks that are stress activated provides a mechanistic framework to characterise the multifaceted nature of weaning stress adaptation in beef calves. Thus, capturing subtle transcriptomic changes provides insight into the molecular mechanisms that underlie the physiological response to weaning stress. Overall design: Examination of a time course (day 0, 1, 2 and 7) for 2 treatments, calves either housed with their dam (control) or housed and simultaneously weaned, using RNA-seq. The supplementary processed data file 'read_counts.txt' contains unnormalized read counts for each Ensembl bovine gene in each of the 48 samples. Unnormalized counts are required for input to EdgeR. Genome build: Btau4.0
Publication Title
Transcriptomic analysis of the stress response to weaning at housing in bovine leukocytes using RNA-seq technology.
Sample Metadata Fields
Specimen part, Disease, Treatment, Subject
View Samples- Homo sapiens
- 24 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Recessive retinitis pigmentosa (RP) is often caused by nonsense mutations that lead to low mRNA levels as a result of nonsense-mediated decay. Some RP genes are expressed at detectable levels in leukocytes as well as in the retina. We designed a microarray-based method to find recessive RP genes based on low lymphoblast mRNA expression levels
Publication Title
Insights from retinitis pigmentosa into the roles of isocitrate dehydrogenases in the Krebs cycle.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 8 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
This study identifies a transciptomic myometrial profile associated with dystocia in spontanous nulliparous term labour
Publication Title
Identification of a myometrial molecular profile for dystocic labor.
Sample Metadata Fields
Sex, Specimen part
View Samples- Saccharomyces cerevisiae
- 27 Downloadable Samples
- Illumina HiSeq 2000
Description
Engineering microbes with novel metabolic properties is a critical step for production of biofuels and biochemicals. Synthetic biology enables identification and engineering of metabolic pathways into microbes; however, knowledge of how to reroute cellular regulatory signals and metabolic flux remains lacking. Here we used network analysis of multi-omic data to dissect the mechanism of anaerobic xylose fermentation, a trait important for biochemical production from plant lignocellulose. We compared transcriptomic, proteomic, and phosphoproteomic differences across a series of strains evolved to ferment xylose under various conditions. Overall design: RNA-seq and transcriptome analysis of three evolved S. cerevisiae strains (Y22-3, Y127, Y128) grown aerobically or anaerobically in rich lab media with glucose, xylose, galactose, or sorbitol. Duplicates were collected on different days.
Publication Title
Rewired cellular signaling coordinates sugar and hypoxic responses for anaerobic xylose fermentation in yeast.
Sample Metadata Fields
Subject
View Samples- Mus musculus
- 16 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Transgenic FVB/NCrl-Tg(GFAP-Mir183,Mir96,Mir182)MDW1 mice (Tg1MDW) overexpress this neurosensory-specific miRNA cluster in the inner ear and were developed as a model system to identify target genes and biologic processes regulated by the miR-183 cluster.
Publication Title
A mouse model of miR-96, miR-182 and miR-183 misexpression implicates miRNAs in cochlear cell fate and homeostasis.
Sample Metadata Fields
Specimen part
View Samples- Saccharomyces cerevisiae
- 16 Downloadable Samples
- Illumina HiSeq 2500
Description
Engineering microbes with novel metabolic properties is a critical step for production of biofuels and biochemicals. Synthetic biology enables identification and engineering of metabolic pathways into microbes; however, knowledge of how to reroute cellular regulatory signals and metabolic flux remains lacking. Here we used network analysis of multi-omic data to dissect the mechanism of anaerobic xylose fermentation, a trait important for biochemical production from plant lignocellulose. We compared transcriptomic, proteomic, and phosphoproteomic differences across a series of strains evolved to ferment xylose under various conditions. Overall design: RNA-seq and transcriptome analysis of Azf1 deletion and over-expression (via MoBY 2.0 plasmid) in YPX -O2. Duplicate samples were collected on different days.
Publication Title
Rewired cellular signaling coordinates sugar and hypoxic responses for anaerobic xylose fermentation in yeast.
Sample Metadata Fields
Subject
View Samples