Filters
Technology
Platform
GSE43798
Mus musculus
10 Downloadable Samples
Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
The following abstract from the submitted manuscript describes the major findings of this work.
Publication Title
A role for peroxisome proliferator-activated receptor γ coactivator-1 in the control of mitochondrial dynamics during postnatal cardiac growth.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 8 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
To understand molecular mechanisms by which reducing Id2 rescues impaired erythropoiesis and hematopoietic progenitor cell development in Gfi-1-/- mice, we compared gene expression in Gfi-1-/-;Id2+/- and Gfi-1-/- BMC using Affymetrix microarray.
Publication Title
Gfi-1 regulates the erythroid transcription factor network through Id2 repression in murine hematopoietic progenitor cells.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 6 Downloadable Samples
Illumina HiSeq 2000
Description
In eukaryotes, the 3'' ends of RNA polymerase II-generated transcripts are made in the majority of cases by site-specific endonucleolytic cleavage, followed by the addition of a poly(A) tail. By alternative polyadenylation, a gene can give rise to multiple mRNA isoforms that differ in the length of their 3'' UTRs and hence in their susceptibility to post-transcriptional regulatory factors such as microRNAs. A series of recently conducted high-throughput studies of poly(A) site usage revealed an extensive tissue-specific control of 3’ UTR length and drastic changes in 3’ UTR length of mRNAs upon induction of proliferation in resting cells. To understand the dynamics of polyadenylation site usage, we recently identified binding sites of the major pre-mRNA 3’ end processing factors - cleavage and polyadenylation specificity factor (CPSF), cleavage stimulation factor (CstF), and cleavage factor Im (CF Im) - and mapped cleaved polyadenylation sites in HEK293 cells. Our present study extends previous findings on the role of CF Im in alternative polyadenylation and reveals that subunits of the CF Im complex generally control 3’ UTR length. More specifically, we demonstrate that the loss-of-function of CF Im68 and CF Im25 but not of CF Im59 leads to a transcriptome-wide increase of the use of proximal polyadenylation sites. Overall design: 3'' ends of transcripts were profiled by high-throughput sequencing in HEK 293 cells under normal conditions, and in HEK 293 cells depleted of 3'' end processing factors CF Im25, CF Im59, and CF Im68.
Publication Title
Cleavage factor Im is a key regulator of 3' UTR length.
Sample Metadata Fields
Cell line, Subject
View Samples- Homo sapiens
- 4 Downloadable Samples
- Illumina HiSeq 2000
Description
Through alternative polyadenylation, human mRNAs acquire longer or shorter 3'' untranslated regions, the latter typically associated with higher transcript stability and increased protein production. To understand the dynamics of polyadenylation site usage, we mapped transcriptome-wide both binding sites of 3'' end processing factors CPSF-160, CPSF-100, CPSF-73, CPSF-30, Fip1, CstF-64, CstF-64tau, CF Im25, CF Im59, and CF Im68 and 3'' end processing sites in HEK293 cells. We found that although binding sites of these factors generally cluster around the poly(A) sites most frequently used in cleavage, CstF-64/CstF-64tau and CF Im proteins have much higher positional specificity compared to CPSF components. Knockdown of CF Im68 induced a systematic use of proximal polyadenylation sites, indicating that changes in relative abundance of a single 3'' end processing factor can modulate the length of 3'' untranslated regions transcriptome-wide, and suggesting a mechanism behind the previously observed increase in tumor cell invasiveness upon CF Im68 knockdown. Overall design: 3'' ends of transcripts were profiled by high-throughput sequencing in HEK 293 cells under normal conditions, and in HEK 293 cells depleted of 3'' end processing factors CF Im 68 and CstF-64.
Publication Title
Genome-wide analysis of pre-mRNA 3' end processing reveals a decisive role of human cleavage factor I in the regulation of 3' UTR length.
Sample Metadata Fields
Cell line, Subject
View Samples- Mus musculus
- 30 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Compelling evidence suggests that mitochondrial dysfunction contributes to the pathogenesis of heart failure, including defects in the substrate oxidation, and the electron transport chain (ETC) and oxidative phosphorylation (OXPHOS). However, whether such changes occur early in the development of heart failure, and are potentially involved in the pathologic events that lead to cardiac dysfunction is unknown. To address this question, we conducted transcriptomic/metabolomics profiling in hearts of mice with two progressive stages of pressure overload-induced cardiac hypetrophy: i) cardiac hypertrophy with preserved ventricular function achieved via transverse aortic constriction for 4 weeks (TAC) and ii) decompensated cardiac hypertrophy or heart failure (HF) caused by combining 4 wk TAC with a small apical myocardial infarction. Transcriptomic analyses revealed, as shown previously, downregulated expression of genes involved in mitochondrial fatty acid oxidation in both TAC and HF hearts compared to sham-operated control hearts. Surprisingly, however, there were very few changes in expression of genes involved in other mitochondrial energy transduction pathways, ETC, or OXPHOS. Metabolomic analyses demonstrated significant alterations in pathway metabolite levels in HF (but not in TAC), including elevations in acylcarnitines, a subset of amino acids, and the lactate/pyruvate ratio. In contrast, the majority of organic acids were lower than controls. This metabolite profile suggests bottlenecks in the carbon substrate input to the TCA cycle. This transcriptomic/metabolomic profile was markedly different from that of mice PGC-1a/b deficiency in which a global downregulation of genes involved in mitochondrial ETC and OXPHOS was noted. In addition, the transcriptomic/metabolomic signatures of HF differed markedly from that of the exercise-trained mouse heart. We conclude that in contrast to current dogma, alterations in mitochondrial metabolism that occur early in the development of heart failure reflect largely post-transcriptional mechanisms resulting in impedance to substrate flux into the TCA cycle, reflected by alterations in the metabolome.
Publication Title
Energy metabolic reprogramming in the hypertrophied and early stage failing heart: a multisystems approach.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Mus musculus
- 199 Downloadable Samples
- Illumina HiSeq 1000
Description
Single-cell RNA-seq analysis of pre- and postnatal mouse endolymphatic sac demonstrates two types of differentiated cells distinguished by their mRNA expression signatures. Overall design: mRNA-seq profiles from 213 single cells from embryonic day 12.5, 16.5, postnatal day 5 and 30 mouse endolymphatic sac were analyzed
Publication Title
Molecular architecture underlying fluid absorption by the developing inner ear.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Homo sapiens
- 9 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Breast tumorigenesis involves modulation of gene expression.
Publication Title
Nucleotide excision repair deficiency is intrinsic in sporadic stage I breast cancer.
Sample Metadata Fields
Specimen part, Subject
View Samples- Mus musculus
- 27 Downloadable Samples
- Affymetrix Mouse Genome 430A 2.0 Array (mouse430a2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Long noncoding RNAs regulate adipogenesis.
Sample Metadata Fields
Specimen part, Disease
View Samples- Mus musculus
- 11 Downloadable Samples
- Affymetrix Mouse Genome 430A 2.0 Array (mouse430a2)
Description
Adipogenesis involves the regulation of hundreds of genes by several well-studied proteins, but the role of long, noncoding RNAs in this process has not been defined. We track the regulation of hundreds of lncRNAs during adipocyte differentiation, and find several that are essential for this process.
Publication Title
Long noncoding RNAs regulate adipogenesis.
Sample Metadata Fields
Specimen part, Disease
View Samples- Mus musculus
- 8 Downloadable Samples
- Illumina Genome Analyzer
Description
Adipogenesis involves the regulation of hundreds of genes by several well-studied proteins, but the role of long, noncoding RNAs in this process has not been defined. We track the regulation of hundreds of lncRNAs during adipocyte differentiation, and find several that are essential for this process. Overall design: We extractedbrown and white primary adipocytes and pre-adipocytes and profiled lncRNA expresssion via mRNA-Seq. We also profiled cultured, differentiated adipocytes to verify that we could recapitulate the adipocyte expression profile in preparation for a loss-of-function screen for essential adipogenic lincRNAs.
Publication Title
Long noncoding RNAs regulate adipogenesis.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples