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SRP116194
Mus musculus
8 Downloadable Samples
NextSeq 500
Description
Single-stranded DNA or RNA sequences rich in guanine (G) can adopt non-canonical structures known as G-quadruplexes (G4). G4 in the mitochondrial genome are heavy-strand enriched and have been associated with the formation of deletion breakpoints that cause mitochondrial diseases. However, the functional role of G4 structures in mitochondria remains unclear. Here, we have identified RHPS4 as a G4-specific ligand that localizes to mitochondria and causes replication pausing, with mitochondrial DNA (mtDNA) depletion occurring at higher dosage. We further show that RHPS4 interferes with mitochondrial transcript elongation at low doses, leading to respiratory complex depletion. These unprecedented observations suggest that G4 motifs modulate mitochondrial transcription and replication efficiency. Using the differential effects of high vs low RHPS4 dosing, we characterized gene expression pathway responses to mitochondrial transcription inhibition or mitochondrial genome depletion. Importantly, a human mtDNA mutation that increases G4 formation potential strongly enhanced the RHPS4-mediated mitochondrial respiratory defect. We propose that abnormal G4 dynamics may contribute to mtDNA instability and gene expression defects, particularly in the presence of mitochondrial mutations that enhance the G4 formation. Overall design: Total RNA was extracted from the mouse embryonic fibroblasts (MEFs) stimulated with 0um (n=3), 2um (n=3), and 10um (n=2) RHPS4. Total stranded RNA libraries (ribo-depleted) were generated and sequenced on the Illumina NextSeq 500 NGS platform. RNA-seq data was analyzed for differentially expressed genes between groups of samples.
Publication Title
G-quadruplex dynamics contribute to regulation of mitochondrial gene expression.
Sample Metadata Fields
Subject
View Samples- Homo sapiens
- 9 Downloadable Samples
Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Spheroids are 3D multi-cell aggregates formed in non-addherent culture conditions. In ovarian cancer (OC), they serve as a vehicle for cancer cell dissemination in the peritoneal cavity. We investigated genes and networks upregulated in three dimensional (3D) versus two-dimensional (2D) culture conditions by Affymetrix gene expression profiling and identified ALDH1A1, a cancer stem cell marker as being upregulated in OC spheroids. Network analysis confirmed ALDH1A1 upregulation in spheroids in direct connection with elements of the -catenin pathway. A parallel increase in the expression levels of -catenin and ALDH1A1 was demonstrated in spheroids vs. monolayers an in successive spheroid generations by using OC cell liness and primary OC cells. The percentage of Aldefluor positive cells was significantly higher in spheroids vs. monolayers in IGROV1, A2780, SKOV3, and primary OC cells. B-catenin knock-down decreased ALDH1A1 expression and chromatin immunoprecipitation demonstrated that -catenin directly binds to the ALDH1A1 promoter. Both siRNA mediated -catenin knock-down and a novel ALDH1A1 small molecule enzymatic inhibitor described here for the first time, decreased the number of OC spheroids (p<0.001) and cell viability. These data strongly support the role of -catenin regulated ALDH1A1 in the maintenance of OC spheroids and of a stem cell phenotype and propose new ALDH1A1 inhibitors targeting this cell population.
Publication Title
β-Catenin-regulated ALDH1A1 is a target in ovarian cancer spheroids.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 380 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Sleep and affective behaviors are highly interrelated phenotypes, commonly altered in a variety of neuropsychiatric diseases, including major depressive disorder (MDD). To understand the transcriptomic organization underlying sleep and affective function, we studied a population of (C57BL/6J x 129S1/SvImJ) F2 mice by measuring 283 affective and sleep phenotypes and profiling gene expression across four brain regions, including the frontal cortex, hippocampus, thalamus, and hypothalamus. We identified converging molecular bases for sleep and affective phenotypes at both the single-gene and gene-network levels. Utilizing publicly available transcriptomic datasets collected from sleep-deprived mice and major depressive disorder (MDD) patients, we identified three cortical gene networks altered by sleep/wake changes and depression. The network-level actions of sleep loss and depression were opposite to each other, providing a mechanistic basis for the sleep disruptions commonly observed in depression as well as the reported acute antidepressant effects of sleep deprivation. We highlight one particular network composed of circadian rhythm regulators and neuronal activity-dependent immediate-early genes. The key upstream driver of this network, Arc, may act as a nexus linking sleep and depression. Our data provide mechanistic insights into the role of sleep in affective function and MDD.
Publication Title
Cross-species systems analysis identifies gene networks differentially altered by sleep loss and depression.
Sample Metadata Fields
Sex, Specimen part
View Samples- Homo sapiens
- 84 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Human papillomaviruses (HPVs) are associated with nearly all cervical cancers (CCs), 20-30% of head and neck cancers (HNCs), and other cancers. Because HNCs also arise in HPV-negative patients, this type of cancer provides unique opportunities to define similarities and differences of HPV-positive versus HPV-negative cancers arising in the same tissue. Here, we describe genome-wide expression profiling of 84 HNCs, CCs and site-matched normal epithelial samples in which we used laser capture microdissection to enrich samples for tumor-derived versus normal epithelial cells. This analysis revealed that HPV+HNCs and CCs differed in their patterns of gene expression yet shared many changes compared to HPV-HNCs. Some of these shared changes were predicted, but many others were not. Notably, HPV+HNCs and CCs were found to be upregulated in their expression of a distinct and larger subset of cell cycle genes than observed in HPV-HNC. Moreover, HPV+ cancers over-expressed testis-specific genes that are normally expressed only in meiotic cells. Many, though not all, of the hallmark differences between HPV+HNC and HPV-HNC were a direct consequence of HPV and in particular the viral E6 and E7 oncogenes. This included a novel association of HPV oncogenes with testes specific gene expression. These findings in primary human tumors provide novel biomarkers for early detection of HPV+ and HPV- cancers, and emphasize the potential value of targeting E6 and E7 function, alone or combined with radiation and/or traditional chemotherapy, in the treatment of HPV+ cancers.
Publication Title
Fundamental differences in cell cycle deregulation in human papillomavirus-positive and human papillomavirus-negative head/neck and cervical cancers.
Sample Metadata Fields
Sex, Age
View Samples- Homo sapiens
- 15 Downloadable Samples
- NextSeq 500
Description
To understand the biological mechanism of ELL2 in multiple myeloma (MM), we show that the MM risk allele lowers ELL2 expression in CD138+ plasma cells (Pcombined=2.5×10-27; bcombined=-0.24 s.d.), but not in peripheral blood or other tissues. Consistent with this, several variants representing the MM risk allele map to regulatory genomic regions, and three yield reduced transcriptional activity in plasmocytoma cell lines. One of these (rs3777189-C) co-locates with the best-supported lead variants for ELL2 expression and MM risk, and reduces binding of MAFF/G/K family transcription factors. Moreover, further analysis reveals that the MM risk allele associates with upregulation of gene sets related to ribosome biogenesis, and knockout/knockdown and rescue experiments in plasmocytoma cell lines support a cause-effect relationship. Overall design: Reconstitution of ELL2 expression in L363-ELL2-knockout cells
Publication Title
The multiple myeloma risk allele at 5q15 lowers ELL2 expression and increases ribosomal gene expression.
Sample Metadata Fields
Specimen part, Disease, Disease stage, Cell line, Treatment, Subject
View Samples- Homo sapiens
- 6 Downloadable Samples
- NextSeq 500
Description
To understand the biological mechanism of ELL2 in multiple myeloma (MM), we show that the MM risk allele lowers ELL2 expression in CD138+ plasma cells (Pcombined=2.5×10-27; bcombined=-0.24 s.d.), but not in peripheral blood or other tissues. Consistent with this, several variants representing the MM risk allele map to regulatory genomic regions, and three yield reduced transcriptional activity in plasmocytoma cell lines. One of these (rs3777189-C) co-locates with the best-supported lead variants for ELL2 expression and MM risk, and reduces binding of MAFF/G/K family transcription factors. Moreover, further analysis reveals that the MM risk allele associates with upregulation of gene sets related to ribosome biogenesis, and knockout/knockdown and rescue experiments in plasmocytoma cell lines support a cause-effect relationship. Overall design: knock out ELL2 in L363 cells using CRISPR-Cas9
Publication Title
The multiple myeloma risk allele at 5q15 lowers ELL2 expression and increases ribosomal gene expression.
Sample Metadata Fields
Disease, Disease stage, Cell line, Subject
View Samples- Homo sapiens
- 15 Downloadable Samples
- Affymetrix Human Gene 2.1 ST Array (hugene21st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Simultaneous analysis of miRNA-mRNA in human meningiomas by integrating transcriptome: A relationship between PTX3 and miR-29c.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Homo sapiens
- 15 Downloadable Samples
- Affymetrix Human Gene 2.1 ST Array (hugene21st)
Description
Although meningioma is a common disease, there is a lack of understanding of the underlying molecular mechanisms behind its initiation and progression. We used combined miRNA-mRNA transcriptome analysis to discover novel genes and networks in meningiomas.
Publication Title
Simultaneous analysis of miRNA-mRNA in human meningiomas by integrating transcriptome: A relationship between PTX3 and miR-29c.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Arabidopsis thaliana
- 6 Downloadable Samples
- Illumina HiSeq 2500, Illumina HiSeq 2000
Description
We report the role of LSM1-7 complex in the Arabidopsis tolerance to abiotic stresses. LSM1-7 controls gene expression reprogramming at the post-transcriptional level by promoting the decapping of mRNA. This function is selectively achieve over selected stress-induced transcripts depending on stress nature. Overall design: Comparison of transcriptomes from Col-0 and lsm1a lsm1b plants exposed to low temperatures, drought or high salt conditions
Publication Title
The LSM1-7 Complex Differentially Regulates Arabidopsis Tolerance to Abiotic Stress Conditions by Promoting Selective mRNA Decapping.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 3 Downloadable Samples
- Affymetrix Human Gene 2.1 ST Array (hugene21st)
Description
Leukemia Inhibitory Factor is an important cytokine of the IL family. Recent findings suggest it has a crucial role in cancer progression
Publication Title
Leukemia Inhibitory Factor Promotes Aggressiveness of Chordoma.
Sample Metadata Fields
Cell line
View Samples