To identify altered pathways in SCA28 LCLs, we performed a whole genome expression profiling, based on Affymetrix Human Genome U133A 2.0 Chip Array, on LCLs from four unrelated patients, each carrying a different AFG3L2 mutation.
Genome-wide expression profiling and functional characterization of SCA28 lymphoblastoid cell lines reveal impairment in cell growth and activation of apoptotic pathways.
Sex, Specimen part
View SamplesNoncoding RNAs (ncRNAs) play increasingly appreciated gene-regulatory roles. Here, we describe a regulatory network centered on four ncRNAs—a long ncRNA, a circular RNA, and two microRNAs—using gene editing in mice to probe the molecular consequences of disrupting key components of this network. The long ncRNA Cyrano uses an extensively paired site to miR-7 to trigger destruction of this microRNA. Cyrano-directed miR-7 degradation is much more efficient than previously described examples of target-directed microRNA degradation, which come primarily from studies of artificial and viral RNAs. By reducing miR-7 levels, Cyrano prevents repression of miR-7–targeted mRNAs and enables the accumulation of Cdr1as, a circular RNA known to regulate neuronal activity. Without Cyrano, excess miR-7 causes cytoplasmic destruction of Cdr1as, in part through enhanced slicing of Cdr1as by a second miRNA, miR-671. Thus, several types of ncRNAs can collaborate to establish a sophisticated regulatory network. Overall design: mRNA expression profiling by RNA-seq of 10 tissues from wild-type (WT) and Cyrano–/– (CyrKO) mice. This study consists of 96 polyA-selected unstranded Tru-seq libraries prepared from 4–6 biological replicates per genotype for each tissue.
A Network of Noncoding Regulatory RNAs Acts in the Mammalian Brain.
Sex, Age, Specimen part, Cell line, Subject
View SamplesNoncoding RNAs (ncRNAs) play increasingly appreciated gene-regulatory roles. Here, we describe a regulatory network centered on four ncRNAs—a long ncRNA, a circular RNA, and two microRNAs—using gene editing in mice to probe the molecular consequences of disrupting key components of this network. The long ncRNA Cyrano uses an extensively paired site to miR-7 to trigger destruction of this microRNA. Cyrano-directed miR-7 degradation is much more efficient than previously described examples of target-directed microRNA degradation, which come from studies of artificial and viral RNAs. By reducing miR-7 levels, Cyrano prevents repression of miR-7–targeted mRNAs and enables the accumulation of Cdr1as, a circular RNA known to regulate neuronal activity. Without Cyrano, excess miR-7 causes cytoplasmic destruction of Cdr1as, in part through enhanced slicing of Cdr1as by a second miRNA, miR-671. Thus, several types of ncRNAs can collaborate to establish a sophisticated regulatory network. Overall design: mRNA expression profiling by RNA-seq of cerebellum and cortex from wild-type (WT), Cyrano miR-7 site mutant (CyrMut), Cyrano–/– (CyrKO), and Mir7a1–/–; Mir7b–/– (Mir7DKO) mice. This study consists of 33 polyA-selected stranded NEXTflex libraries prepared from 3-4 biological replicates for each tissue and each genotype. To minimize batch effects, libraries for wild-type tissues were prepared and sequenced for each experiment and only intra-experiment comparisons were made.
A Network of Noncoding Regulatory RNAs Acts in the Mammalian Brain.
Sex, Age, Specimen part, Cell line, Subject
View SamplesRecent studies have reported that competitive endogenous RNAs (ceRNAs) can act as sponges for a miRNA through their binding sites and that changes in ceRNA abundances from individual genes can modulate the miRNA’s activity. Consideration of this hypothesis would benefit from knowing the quantitative relationship between a miRNA and its endogenous target sites. Here, we altered intracellular target-site abundance through expression of a miR-122 target in hepatocytes and livers, and analyzed the effects on miR-122 target genes. Target repression was released in a threshold-like manner at high target-site abundance (=1.5x10^5 added target sites per cell), and this threshold was insensitive to the effective levels of the miRNA. Furthermore, in response to extreme metabolic liver disease models, global target-site abundance of hepatocytes did not change sufficiently to affect miRNA-mediated repression. Thus, modulation of miRNA target abundance is unlikely to cause significant effects on gene expression and metabolism through a ceRNA effect. Overall design: Seventeen mRNA profiles were generated of 1) primary hepatocytes of mice expressing variable levels of a recombinant Adenovirus expressing the transcript of AldolaseA (Ad-AldoA), containing either 1 or 3 sites matching miR-122 or a mutated miR-122 site (no site), 2) primary hepatocytes derived from mice treated with Antagomir-122 (treatment group) or Antagomir-122mm (control group), 3) livers originating of a genetic model (Ldlr deficient mice) causing severe pathological changes in cholesterol metabolism, 4) livers of mice perfused with Insulin or PBS, and 5) livers of mice fed a high-fat or chow diet; most samples were sequenced in duplicate or triplicate by an Illumina HiSeq 2000. One small RNA profile was also generated from livers of mice fed a chow diet by Solexa sequencing.
Assessing the ceRNA hypothesis with quantitative measurements of miRNA and target abundance.
No sample metadata fields
View SamplesGSE2240 contains two different experimental subsets:
Functional profiling of human atrial and ventricular gene expression.
No sample metadata fields
View SamplesWe applied a novel approach of parallel transcriptional analysis of multiple, highly fractionated stem and progenitor populations in a genetically defined subset of AML (AML with monosomy 7). We isolated phenotypic long-term HSC (LT-HSC), short-term HSC (ST-HSC), and committed granulocyte-monocyte progenitors (GMP) from individual patients with AML, and measured gene expression profiles of each population, and in comparison to their phenotypic counterparts from age-matched healthy controls.
Overexpression of IL-1 receptor accessory protein in stem and progenitor cells and outcome correlation in AML and MDS.
Age, Specimen part
View SamplesWe applied a novel approach of parallel transcriptional analysis of multiple, highly fractionated stem and progenitor populations from patients with acute myeloid leukemia (AML) and a normal karyotype. We isolated phenotypic long-term HSC (LT-HSC), short-term HSC (ST-HSC), and committed granulocyte-monocyte progenitors (GMP) from individual patients, and measured gene expression profiles of each population, and in comparison to their phenotypic counterparts from age-matched healthy controls.
Overexpression of IL-1 receptor accessory protein in stem and progenitor cells and outcome correlation in AML and MDS.
Age, Specimen part
View SamplesRight ventricular failure (RVF) due to pressure load is a major cause of death in congenital heart diseases and pulmonary hypertension. The mechanisms of RVF are yet unknown. Research is hampered by the lack of a good RVF model. Our aim was to study the pathophysiology of RVF in a rat model of chronic pressure load.
Clinical symptoms of right ventricular failure in experimental chronic pressure load are associated with progressive diastolic dysfunction.
Sex, Specimen part
View SamplesIdentification of differentially expressed genes upon treatment with Eltrombopag in HL60 cells. HL60 cells were untreated, or treated with 3ug/ml of Eltrombopag for 36 hrs in RPMI with 10% FBS
Eltrombopag inhibits the proliferation of leukemia cells via reduction of intracellular iron and induction of differentiation.
Specimen part, Cell line
View SamplesThis SuperSeries is composed of the SubSeries listed below.
H2.0-like homeobox regulates early hematopoiesis and promotes acute myeloid leukemia.
Specimen part, Cell line
View Samples