Use existing public data, cell lines and patient tumors with a personalized medicine approach to predict effective therapies for treatment of Neurofibroma tumors.
Molecular-guided therapy predictions reveal drug resistance phenotypes and treatment alternatives in malignant peripheral nerve sheath tumors.
Specimen part
View SamplesOriginal patient tumor is directly implanted in mice xenografts. Tumor is propagated to multiple mice for conduct of 6 arm treatment trials and control. Therapies are selected based on T0 and F0 genomic profiles.
Using a rhabdomyosarcoma patient-derived xenograft to examine precision medicine approaches and model acquired resistance.
No sample metadata fields
View SamplesThe floxed insulin receptor was specifically targetted for deletion in the mammary gland using a mouse strain bearing Cre recombinase under the BLG promoter.
The insulin receptor plays an important role in secretory differentiation in the mammary gland.
Specimen part
View SamplesThe pervasive nature of RNA polymerase II (Pol II) transcription requires efficient termination. A key player in this process is the cleavage and polyadenylation (CPA) factor PCF11, which directly binds to the Pol II C-terminal domain and dismantles elongating Pol II from DNA in vitro. We demonstrate that PCF11-mediated termination is essential for vertebrate development. A range of genomic analyses, including: mNET-seq, 3' mRNA-seq, chromatin RNA-seq and ChIP-seq, reveals that PCF11 enhances transcription termination and stimulates early polyadenylation genome-wide. PCF11 binds preferentially between closely spaced genes, where it prevents transcriptional interference and downstream gene silencing. Notably, PCF11 is sub-stoichiometric to the CPA complex. Low levels of PCF11 are maintained by an auto-regulatory mechanism involving premature termination of its own transcript, and are important for normal development. Both in human cell culture and during zebrafish development, PCF11 selectively attenuates the expression of other transcriptional regulators by premature CPA and termination. Overall design: Semi-nascent transcriptome measured by chromatin-bound RNA-seq in HeLa cells. Control and PCF11 knock-down (2 biological replicates) and control and PCF11 PAS1 deletion (4 biological replicates).
Selective Roles of Vertebrate PCF11 in Premature and Full-Length Transcript Termination.
Specimen part, Subject
View SamplesThe pervasive nature of RNA polymerase II (Pol II) transcription requires efficient termination. A key player in this process is the cleavage and polyadenylation (CPA) factor PCF11, which directly binds to the Pol II C-terminal domain and dismantles elongating Pol II from DNA in vitro. We demonstrate that PCF11-mediated termination is essential for vertebrate development. A range of genomic analyses, including: mNET-seq, 3' mRNA-seq, chromatin RNA-seq and ChIP-seq, reveals that PCF11 enhances transcription termination and stimulates early polyadenylation genome-wide. PCF11 binds preferentially between closely spaced genes, where it prevents transcriptional interference and downstream gene silencing. Notably, PCF11 is sub-stoichiometric to the CPA complex. Low levels of PCF11 are maintained by an auto-regulatory mechanism involving premature termination of its own transcript, and are important for normal development. Both in human cell culture and during zebrafish development, PCF11 selectively attenuates the expression of other transcriptional regulators by premature CPA and termination. Overall design: 3' mRNA-seq in individual zebrafish embryo heads. Two types of mutants: zPCF11 null and zPCF11 with deletion of PAS1. Wild-type (wt, +/+), heterozygous (het, +/-) and homozygous mutant (hom, -/-) embryos were analyzed. Wild-type and heterozygous animals were phenotypically indistinguishable.
Selective Roles of Vertebrate PCF11 in Premature and Full-Length Transcript Termination.
Subject
View SamplesThe pervasive nature of RNA polymerase II (Pol II) transcription requires efficient termination. A key player in this process is the cleavage and polyadenylation (CPA) factor PCF11, which directly binds to the Pol II C-terminal domain and dismantles elongating Pol II from DNA in vitro. We demonstrate that PCF11-mediated termination is essential for vertebrate development. A range of genomic analyses, including: mNET-seq, 3' mRNA-seq, chromatin RNA-seq and ChIP-seq, reveals that PCF11 enhances transcription termination and stimulates early polyadenylation genome-wide. PCF11 binds preferentially between closely spaced genes, where it prevents transcriptional interference and downstream gene silencing. Notably, PCF11 is sub-stoichiometric to the CPA complex. Low levels of PCF11 are maintained by an auto-regulatory mechanism involving premature termination of its own transcript, and are important for normal development. Both in human cell culture and during zebrafish development, PCF11 selectively attenuates the expression of other transcriptional regulators by premature CPA and termination. Overall design: 3' mRNA-seq in HeLa cells. Control and PCF11 knock-down (4 biological replicates); control and PCF11 PAS1 deletion clones muA and muB (3 biological replicates); control and additional PCF11 PAS1 deletion clones muC and muD (1 replicate).
Selective Roles of Vertebrate PCF11 in Premature and Full-Length Transcript Termination.
Subject
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Sarcoma Cell Line Screen of Oncology Drugs and Investigational Agents Identifies Patterns Associated with Gene and microRNA Expression.
Specimen part, Cell line
View SamplesCharacterization of 68 cell lines derived from human sarcoma and 5 normal counterpart cells, including drug sensitivity testing, gene expression profiling and microRNA expression profiling have been completed. Data and tools for searching these data will be made publicly available through the NCI Developmental Therapeutics Program. The raw data (.cel files ) are provided through the GEO website. Sarcoma represents a variety of cancers at arise from cells of mesenchymal origin and have seen limited treatment advances in the last decade. Drug sensitivity data coupled with the transcription and microRNA profiles of a cohort of sarcoma cell lines may help define novel treatment paradigms.
Sarcoma Cell Line Screen of Oncology Drugs and Investigational Agents Identifies Patterns Associated with Gene and microRNA Expression.
No sample metadata fields
View SamplesGene expression from pre- and post- Cediranib treated patients with metastatic Alveolar Soft Part Sarcoma (ASPS)
Cediranib for metastatic alveolar soft part sarcoma.
Time
View SamplesAn inducible program of inflammatory gene expression is central to antimicrobial defenses. This response is controlled by a collaboration involving signal-dependent activation of transcription factors, transcriptional co-regulators, and chromatin-modifying factors. We have identified a long noncoding RNA (lncRNA) that acts as a key regulator of this inflammatory response. Pattern recognition receptors such as the Toll-like receptors induce the expression of numerous lncRNAs. One of these, lincRNA-Cox2, mediates both the activation and repression of distinct classes of immune genes. Transcriptional repression of target genes is dependent on interactions of lincRNA-Cox2 with heterogeneous nuclear ribonucleoprotein A/B and A2/B1. Collectively, these studies unveil a central role of lincRNA-Cox2 as a broad-acting regulatory component of the circuit that controls the inflammatory response Overall design: Examination of Mus musculus (C57BL/6 background) gene expression changes following stimulation with Pam3Cys4 in presence or absence of shRNA specifically targetting lncRNA-COX2
A long noncoding RNA mediates both activation and repression of immune response genes.
Specimen part, Cell line, Subject
View Samples