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SRP194050
Mus musculus
4 Downloadable Samples
Illumina HiSeq 2500
Description
gene expression study on brain and lung under Dip2a regulation to better understand the role of Dip2a gene during mice brain and lung development.
Publication Title
Large genomic fragment deletions and insertions in mouse using CRISPR/Cas9.
Sample Metadata Fields
Sex, Specimen part, Cell line
View Samples- Caenorhabditis elegans
- 65 Downloadable Samples
- Illumina HiSeq 2500
Description
Multiple division cycles without growth are a characteristic feature of early embryogenesis. The female germline deposits proteins and RNAs into oocytes to support these divisions, which lack many of the quality control mechanisms operating in somatic cells undergoing growth. How the composition of the oocyte maternal load is regulated to ensure its ability to support early embryogenesis is not known. Here we describe a small RNA-Argonaute pathway, operating in the C. elegans germline, that ensures early embryonic divisions by employing catalytic slicing activity to broadly tune, instead of silence, germline gene expression. Misregulation of one target, a kinesin-13 microtubule depolymerase, underlies a major embryonic phenotype associated with pathway loss. Tuning of target expression is guided by small RNA density, which must ultimately be related to target sequence. Thus, C. elegans employs a single catalytic Argonaute for small RNA-mediated tuning of the mRNA levels of germline-expressed genes that support early embryogenesis. Overall design: mRNA profiling of 2 replicates each for 3 genotypes of adult-stage C. elegans worms
Publication Title
A Small RNA-Catalytic Argonaute Pathway Tunes Germline Transcript Levels to Ensure Embryonic Divisions.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Mus musculus
- 15 Downloadable Samples
Affymetrix Murine Genome U74A Version 2 Array (mgu74av2)
Description
STAT5A and STAT5B proteins belong to the family of signal transducers and activators of transcription. They are encoded by 2 separate genes with 91% identity in their amino acid sequences. Despite their high degree of conservation, STAT5A and STAT5B exert non-redundant functions, resulting at least in part from differences in target gene activation. To better characterize the differential contribution of STAT5A and STAT5B in gene regulation, we performed single or double knock-down of STAT5A and STAT5B using small interfering RNA. Subsequent gene expression profiling and RT-qPCR analyses of IL-3-stimulated Ba/F3-beta cells led to the identification of putative novel STAT5 target genes. Chromatin immunoprecipitation assays analyzing the corresponding gene loci identified unusual STAT5 binding sites compared to conventional STAT5 responsive elements. Some of the STAT5 targets identified are upregulated in several human cancers, suggesting that they might represent potential oncogenes in STAT5-associated malignancies.
Publication Title
In vivo identification of novel STAT5 target genes.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 18 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
These data provide scientific information to understand the mechanism of action of lapatinib resistance in HER2-positive patients and to test the combination of HER2-targeted agents and GSK1363089 (foretinib) in the clinic by using an acquired lapatinib-resistant cell line.
Publication Title
Novel mechanism of lapatinib resistance in HER2-positive breast tumor cells: activation of AXL.
Sample Metadata Fields
Specimen part, Cell line, Treatment
View Samples- Mus musculus
- 10 Downloadable Samples
- Illumina HiSeq 2500
Description
We sought to determine whether Ldh activity in SCC tumors is a marker of the cell type from which these cells arise, or a key metabolic activity important for tumor initiation or progression. Here we show that genetic abrogation of Ldh enzyme activity in HFSC-mediated tumorigenesis had no effect on tumor number, time to tumor formation, tumor proliferation, epithelial to mesenchymal transition in tumors, gene expression in tumors, tumor pathology, or the immune response to tumors. Overall design: Examination of mRNA profile of five LDHA knockout mice vs five wild type (WT) mice using Illumina HiSeq2500.
Publication Title
Increased lactate dehydrogenase activity is dispensable in squamous carcinoma cells of origin.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 5 Downloadable Samples
- IlluminaHiSeq2000
Description
Human pluripotent stem cells (hPSCs) require precise control of post-transcriptional RNA networks to maintain proliferation and survival. Using a recently developed enhanced UV crosslinking and immunoprecipitation (eCLIP) approach, we identify RNA targets of the IMP/IGF2BP family of RNA-binding proteins in hPSCs. At the broad region- and binding site-level IMP1 and IMP2 show reproducible binding to a large and overlapping set of 3''UTR-enriched targets. RNA Bind-N-Seq applied to recombinant full-length IMP1 and IMP2 reveals CA-rich motifs that are enriched in eCLIP-defined binding sites. We observe that IMP1 loss in hPSCs recapitulates IMP1 phenotypes, including a reduction in cell adhesion and an increase in cell death. For cell adhesion, in hPSCs we find IMP1 maintains levels of integrin mRNA, specifically regulating RNA stability of ITGB5. Additionally, we show IMP1 can be linked to hPSC survival via direct target BCL2. Thus, transcriptome-wide binding profiles identify hPSC targets modulating well-characterized IMP1 roles. Overall design: eCLIP-seq was performed in biological replicate for IGF2BP1/IMP1 and IGF2BP2/IMP2, as well as one replicate each for IGF2BP3/IMP3, RBFOX2, and an IgG control. Each sample has a size-matched input control for analysis
Publication Title
Enhanced CLIP Uncovers IMP Protein-RNA Targets in Human Pluripotent Stem Cells Important for Cell Adhesion and Survival.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 6 Downloadable Samples
Description
In this study, we report that HCMV infection results in widespread alternative splicing (AS), shorter 3'-untranslated regions (3'UTRs) and polyA tail lengthening in host genes and CPEB1 depletion reverses infection-related post-transcriptional changes. Overall design: We performed RNA-seq for Mock (Non-targeting siRNA), human Cytomegalovirus (HCMV) with non-targeting siRNA, and CPEB1 siRNA treated human foreskin fibroblasts (HFFs). We also performed RNA-seq for lentivirus mediated GFP overexpression (OE) and CPEB1 overexpression human foreskin fibroblasts. Lastly, we performed TAIL-seq for Mock (Non-targeting siRNA), human Cytomegalovirus (HCMV) with non-targeting siRNA, and CPEB1 siRNA treated HFFs.
Publication Title
RNA-binding protein CPEB1 remodels host and viral RNA landscapes.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 9 Downloadable Samples
- Illumina HiSeq 2000
Description
The inhibitor of DNA binding 2 (Id2) is essential for NK cell development with its canonical role in this pathway being to antagonize E-proteins, silencing E-box gene expression and subsequent commitment to the T and B cell lineages. However, how E-box genes prevent NK cell development and homeostasis remains enigmatic. Here we identify a key role for Id2 in regulating the threshold for IL-15 receptor signaling and homeostasis of NK cells by repressing multiple E-protein target genes including Socs3. Deletion of Id2 in mature NK cells was incompatible with their homeostasis due to impaired IL-15 receptor signaling. Id2-null NK cells displayed impaired IL-15 mediated JAK1/STAT5 phosphorylation, compromised metabolic function and enhanced apoptosis. Remarkably, Id2-null NK cell homeostasis could be fully rescued in vivo by IL-15 receptor stimulation and partially rescued by genetic ablation of Socs3. During normal NK cell maturation we observed an inverse correlation between the expression levels of E-protein target genes and Id2. These results shift the current paradigm on the role of Id2, indicating that it is not only required to antagonize E-proteins during NK cell commitment, but constantly required to titrate E-protein activity to regulate NK cell fitness and responsiveness to IL-15. Overall design: Transcriptional profiling of wild type and Id2-null natural killer (NK) cells using RNA sequencing
Publication Title
The Helix-Loop-Helix Protein ID2 Governs NK Cell Fate by Tuning Their Sensitivity to Interleukin-15.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Homo sapiens
- 46 Downloadable Samples
- Illumina HiSeq 2000
Description
Introduction: Mammalian target of rapamycin (mTOR) represents a key downstream intermediate for a myriad of oncogenic receptor tyrosine kinases. In the case of the insulin-like growth factor (IGF) pathway, the mTOR complex (mTORC1) mediates IGF-1 receptor (IGF-1R)-induced estrogen receptor alpha (ERa) phosphorylation/activation and leads to increased proliferation and growth in breast cancer cells. As a result, the prevalence of mTOR inhibitors combined with hormonal therapy has increased in recent years. Conversely, activated mTORC1 provides negative feedback regulation of IGF signaling via insulin receptor substrate (IRS)-1/2 serine phosphorylation and subsequent proteasomal degradation. Thus, the IGF pathway may provide escape (e.g. de novo or acquired resistance) from mTORC1 inhibitors. It is therefore plausible that combined inhibition of mTORC1 and IGF-1R for select subsets of ER-positive breast cancer patients presents as a viable therapeutic option. Methods: Using hormone-sensitive breast cancer cells stably transfected with the aromatase gene (MCF-7/AC-1), works presented herein describe the in vitro and in vivo antitumor efficacy of the following compounds: dalotuzumab (DALO; “MK-0646”; anti-IGF-1R antibody), ridaforolimus (RIDA; “MK-8669”; mTORC1 small molecule inhibitor) and letrozole (“LET”, aromatase inhibitor). Results: With the exception of MK-0646, all single agent and combination treatment arms effectively inhibited xenograft tumor growth, albeit to varying degrees. Correlative tissue analyses revealed MK-0646 alone and in combination with LET induced insulin receptor alpha A (InsR-A) isoform upregulation (both mRNA and protein expression), thereby further supporting a triple therapy approach. Conclusion: These data provide preclinical rationalization towards the combined triple therapy of LET plus MK-0646 plus MK-8669 as an efficacious anti-tumor strategy for ER-positive breast tumors. Overall design: 46 samples, 28 days post treatment
Publication Title
Ridaforolimus (MK-8669) synergizes with Dalotuzumab (MK-0646) in hormone-sensitive breast cancer.
Sample Metadata Fields
Cell line, Treatment, Subject, Time
View Samples- Mus musculus
- 14 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
This study was designed to define erythropoietin (EPO) regulated genes in murine bone marrow erythroid progenitor cells at two stages of development, designated E1, and E2. E1 cells correspond to CFUe- like progenitors, while E2 cells are proerythroblasts.
Publication Title
Defining an EPOR- regulated transcriptome for primary progenitors, including Tnfr-sf13c as a novel mediator of EPO- dependent erythroblast formation.
Sample Metadata Fields
Sex, Specimen part, Treatment
View Samples