Filters
Technology
Platform
GSE57761
Mus musculus
5 Downloadable Samples
Affymetrix Mouse Gene 2.0 ST Array (mogene20st)
Description
Somatic mitochondrial DNA (mtDNA) mutations contribute to the pathogenesis of age-related disorders, including myelodysplastic syndromes (MDS). The accumulation of mitochondria harboring mtDNA mutations in patients with these disorders suggests a failure of normal mitochondrial quality-control systems. The mtDNA-mutator mice acquire somatic mtDNA mutations via a targeted defect in the proofreading function of the mtDNA polymerase, PolgA, and develop macrocytic anemia similar to that of patients with MDS. We observed an unexpected defect in clearance of dysfunctional mitochondria at specific stages during erythroid maturation in hematopoietic cells from aged mtDNA-mutator mice. Mechanistically, aberrant activation of mechanistic target of rapamycin signaling and phosphorylation of uncoordinated 51-like kinase (ULK) 1 in mtDNA-mutator mice resulted in proteasome mediated degradation of ULK1 and inhibition of autophagy in erythroid cells. To directly evaluate the consequence of inhibiting autophagy on mitochondrial function in erythroid cells harboring mtDNA mutations in vivo, we deleted Atg7 from erythroid progenitors of wildtype and mtDNA-mutator mice. Genetic disruption of autophagy did not cause anemia in wild-type mice but accelerated the decline in mitochondrial respiration and development of macrocytic anemia in mtDNA-mutator mice. These findings highlight a pathological feedback loop that explains how dysfunctional mitochondria can escape autophagy-mediated degradation and propagate in cells predisposed to somatic mtDNA mutations, leading to disease.
Publication Title
Mito-protective autophagy is impaired in erythroid cells of aged mtDNA-mutator mice.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 16 Downloadable Samples
Illumina HiSeq 2500
Description
The differential gene expression of human cardiomyocytes induced by kinase inhibitors sorafenib and sunitinib is measured by a high-throughput mRNA-sequencing approach called 3''-DGE, that is based on a 3'' end-focused reference sequence library and a transcript molecule counting method with unique molecular identifiers (UMI) for correcting PCR bias. Overall design: Cells were treated with sunitinib, sorafenib, or vehicle control for 48 hours, and gene expression levels of all samples were measured by 3''-DGE and conventional random-primed mRNA-sequencing methods using paired-end reading to obtain the genome-wide expression profiles for each sample.
Publication Title
A Comparison of mRNA Sequencing with Random Primed and 3'-Directed Libraries.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 58 Downloadable Samples
- IlluminaGenomeAnalyzerII, IlluminaGenomeAnalyzer
Description
Noncoding RNAs (ncRNAs) are emerging as key molecules in human cancer, with the potential to serve as novel markers of disease and to reveal uncharacterized aspects of tumor biology. Here we discover 121 unannotated prostate cancer–associated ncRNA transcripts (PCATs) by ab initio assembly of high-throughput sequencing of polyA+ RNA (RNA-Seq) from a cohort of 102 prostate tissues and cells lines. We characterized one ncRNA, PCAT-1, as a prostate-specific regulator of cell proliferation and show that it is a target of the polycomb repressive complex 2 (PRC2). We further found that patterns of PCAT-1 and PRC2 expression stratified patient tissues into molecular subtypes distinguished by expression signatures of PCAT-1–repressed target genes. Taken together, our findings suggest that PCAT-1 is a transcriptional repressor implicated in a subset of prostate cancer patients. These findings establish the utility of RNA-Seq to identify disease-associated ncRNAs that may improve the stratification of cancer subtypes. Overall design: 21 prostate cell lines sequenced on the Illumina Genome Analyzer and GAII. Variable number of replicates per sample. RNA-Seq data from prostate cancer tissues used in this study will be made available on dbGAP.
Publication Title
Transcriptome sequencing across a prostate cancer cohort identifies PCAT-1, an unannotated lincRNA implicated in disease progression.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 10 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
miR-503 represses human cell proliferation and directly targets the oncogene DDHD2 by non-canonical target pairing.
Sample Metadata Fields
Cell line
View Samples- Mus musculus
- 34 Downloadable Samples
- Illumina HiScanSQ
Description
RNA sequencing was performed on proliferating and differentiating wildtype and emerin-null myogenic progenitors to identify molecular pathways implicated in Emery-Dreifuss Muscular Dystrophy. Overall design: Total RNA was isolated from 2 million wildtype or emerin-null H2Ks during proliferation and at each day of differentiation using the miRNeasy Mini Kit (Qiagen, product #217004) and processed according to manufacturer's protocol. RNA was isolated from three independent cell culture plates for each sample.
Publication Title
Expression Profiling of Differentiating Emerin-Null Myogenic Progenitor Identifies Molecular Pathways Implicated in Their Impaired Differentiation.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Homo sapiens
- 8 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
MiR-191 Regulates Primary Human Fibroblast Proliferation and Directly Targets Multiple Oncogenes.
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 10 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
Gene expression profile following transfection with miR-503, miR-103, or miR-494 mature duplex
Publication Title
miR-503 represses human cell proliferation and directly targets the oncogene DDHD2 by non-canonical target pairing.
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 8 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
Profile of transcripts isolated from Ago2 immunoprecipitation following transfection with miR-191 mature duplex and gene expression profile following transfection with miR-191 mature duplex
Publication Title
MiR-191 Regulates Primary Human Fibroblast Proliferation and Directly Targets Multiple Oncogenes.
Sample Metadata Fields
Cell line
View Samples- Saccharomyces cerevisiae
- 4 Downloadable Samples
- Illumina HiSeq 2500
Description
We report quantitative transcriptome data in WT and CHD1 mutant. Overall design: RNA-seq in wild-type and CHD1 mutant.
Publication Title
The ATP-dependent chromatin remodeler Chd1 is recruited by transcription elongation factors and maintains H3K4me3/H3K36me3 domains at actively transcribed and spliced genes.
Sample Metadata Fields
Subject
View Samples- Homo sapiens
- 3 Downloadable Samples
- IlluminaGenomeAnalyzerII
Description
Next Generation Sequencing technologies have enabled de novo gene fusion discovery that could reveal candidates with therapeutic significance in cancer. Here we present an open-source software package, ChimeraScan, for the discovery of chimeric transcription between two independent transcripts. Overall design: Three cancer cell lines with known gene fusions
Publication Title
ChimeraScan: a tool for identifying chimeric transcription in sequencing data.
Sample Metadata Fields
No sample metadata fields
View Samples