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Homo sapiens
6 Downloadable Samples
Affymetrix Human Gene 2.0 ST Array (hugene20st)
Description
Microarray gene expression profiling reveals that PHGDH inhibition by NCT-503 activates a metabolic stress response characterized by downregulation of cell cycle genes and induction of stress response genes.
Publication Title
Metabolic Reprogramming by MYCN Confers Dependence on the Serine-Glycine-One-Carbon Biosynthetic Pathway.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Drosophila melanogaster
- 50 Downloadable Samples
Illumina HiSeq 2500
Description
Proteome and transcriptome often show poor correlation, hindering the system-wide analysis of post-transcriptional regulation. Here, the authors study proteome and transcriptome dynamics during Drosophila embryogenesis and present basic mathematical models describing the temporal regulation of most protein-RNA pairs. Overall design: Whole embryos of Drosophila melanogaster measured at 14 time points during the first 20h of development (0h, 1h, 2h, 3h, 4h, 5h, 6h, 8h, 10h, 12h, 14h, 16h, 18h, 20h). Each sample was measured in biological quadruplicates. RNAseq samples correspond to proteome measurements deposited in ProteomeXchange as PXD005713.
Publication Title
Quantifying post-transcriptional regulation in the development of Drosophila melanogaster.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples
SRP066231- Mus musculus
- 77 Downloadable Samples
- Illumina HiSeq 2500
Description
High temporal resolution RNAseq timecourse of mouse ES differentiation Investigations of transcriptional responses during developmental transitions typically use time courses with intervals that are not commensurate with the timescales of known biological processes. Moreover, such experiments typically focus on protein-coding transcripts, ignoring the important impact of long noncoding RNAs. We evaluated coding and noncoding expression dynamics at unprecedented temporal resolution (6-hourly) in differentiating mouse embryonic stem cells and report the effects of increased temporal resolution on the characterization of the underlying molecular processes. Overall design: Biological duplicate 120 hours of undirected mouse ES cell differentiation sampled 6 hourly Biological duplicate, low passage number (P18) W9.5 ESCs were cultured and differentiated as described previously [PMID:18562676; 17286599]. Cultures were harvested every six hours from the induction of differentiation to 120 hours post differentiation induction. Total RNA from cultures was purified using Trizol (Life Technologies) and DNase treatment was performed by RQ1 DNase (Promega) according to the manufacturer’s instructions. RNA integrity was measured on a Bioanalyzer RNA Nano chip (Agilent). RNA-Seq library preparation and sequencing of Poly-A-NGS libraries generated from 500 ng total RNA using SureSelect Strand Specific RNA Library Preparation Kit (Agilent) according to the manufacturer’s instructions. Paired-end libraries were sequenced to the first 100 bp on a HiSeq 2500 (Illumina) on High Output Mode. Library sequencing quality was determined using FastQC (Babraham Bioinformatics) and FastQ Screen (Babraham Bioinformatics). Illumina adaptor sequence and low quality read trimming (read pair removed if < 20 base pairs) was performed using Trim Galore! (Babraham Bioinformatics: www.bioinformatics.babraham.ac.uk/). Tophat2 [PMID:23618408] was used to align reads to the December 2011 release of the mouse reference genome (mm10) as outlined by Anders et al.[PMID:23975260]. Read counts data corresponding to GENCODE vM2 transcript annotations were generated using HTSeq[PMID:25260700]. All analyses were performed in the R Statistical Environment [PMID:18000755]. Briefly, counts data were background corrected and normalized for library size using edgeR [PMID:19910308], then transformed using voom[PMID:24485249] for differential expression analysis using LIMMA[PMID: 16646809].
Publication Title
High resolution temporal transcriptomics of mouse embryoid body development reveals complex expression dynamics of coding and noncoding loci.
Sample Metadata Fields
Specimen part, Cell line, Subject, Time
View Samples- Mus musculus
- 42 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
The macrophage-Brucella interaction is critical for the establishment of a chronic Brucella infection. Smooth virulent B. suis strain 1330 (S1330) prevents macrophage cell death. However, rough attenuated B. suis strain VTRS1 induces strong macrophage cell death. To further investigate the mechanism of VTRS1-induced macrophage cell death, microarrays were used to analyze temporal transcriptional responses of murine macrophage-like J774. A1 cells infected with S1330 or VTRS1.
Publication Title
Proinflammatory caspase-2-mediated macrophage cell death induced by a rough attenuated Brucella suis strain.
Sample Metadata Fields
Cell line, Treatment
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
MEIS2 has an important role in development and organogenesis, and is implicated in the pathogenesis of human cancer. The molecular basis of MEIS2 action in tumorigenesis is not clear. Here, we show that MEIS2 is highly expressed in human neuroblastoma cell lines and is required for neuroblastoma cell survival and proliferation. Depletion of MEIS2 in neuroblastoma cells leads to M phase arrest and mitotic catastrophe, whereas ectopic expression of MEIS2 markedly enhances neuroblastoma cell proliferation, anchorage-independent growth, and tumorigenicity. Gene expression profiling reveals an essential role of MEIS2 in maintaining the expression of a large number of late cell cycle genes, including those required for DNA replication, G2-M checkpoint control and M phase progression. Importantly, we identify MEIS2 as a transcription activator of the MuvB-BMYB-FOXM1 complex that functions as a master regulator of mitotic gene expression. Further, we show that FOXM1 is a direct target gene of MEIS2 and is required for MEIS2 to upregulate mitotic genes. These findings link a development gene to the control of cell cycle progression and suggest that high MEIS2 expression is a molecular mechanism for high expression of mitotic genes that is commonly observed in cancers of poor prognosis.
Publication Title
MEIS2 is essential for neuroblastoma cell survival and proliferation by transcriptional control of M-phase progression.
Sample Metadata Fields
Cell line, Treatment
View Samples- Mus musculus
- 11 Downloadable Samples
- Affymetrix Murine Genome U74A Version 2 Array (mgu74av2)
Description
Embryonic stem (ES) cells and ES cell-derived progeny characterized by nestin expression (including neural progenitors) were studied (three independent experiments). The mouse ES cell line R1 was cultured on a feeder layer of mouse embryonic fibroblasts (FL). ES cells were differentiated into nestin-positive cells for 4+8 days and 4+11 days according to the differentiation protocol by Rolletschek et al. (Mechanisms of Development 105, 93-104, 2001).
Publication Title
Pluripotency associated genes are reactivated by chromatin-modifying agents in neurosphere cells.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 8 Downloadable Samples
- IlluminaHiSeq2000
Description
Gene splicing requires three basal genetic elements; the 3’ and 5’ splice sites and the branchpoint to which the 5’ intron termini is ligated to form a closed lariat during the splicing reaction. The 5’ and 3’ splice sites that define exon boundaries have been widely identified, revealing pervasive transcription and splicing of human genes. However, the locations of the third requisite element, the branchpoint, are still largely unknown. Here we employ two complementary approaches, targeted RNA sequencing and exoribonuclease digestion, to distil sequenced reads that traverse the lariat junction and, via non-conventional alignment, locate human branchpoint nucleotides. Alignments identify 88,748 branchpoints that correspond to 20% of known introns, with 76% supported by diagnostic sequence mismatch errors. This affords a first genome-wide analysis of branchpoints, describing their distribution, selection, and the existence of a diverse array of overlapping sequence motifs with distinct usage, evolutionary histories, and co-variation with distal splicing elements. The overlap of branchpoints with noncoding human genetic variation also indicates a notable contribution to disease. This annotation and analysis incorporates branchpoints into transcriptomic research and reflects a core role for this element in the regulatory code that governs gene splicing and expression. Overall design: RNaseR validation of branchpoint nucleotides
Publication Title
Genome-wide discovery of human splicing branchpoints.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Abnormal NF-kB2 activation has been reported in several types of human leukemia and lymphomas although the exact mechanisms and affected pathways are not clear. We have investigated these questions through the use of a unique transgenic mouse model with lymphocyte-targeted expression of p80HT, a lymphoma associated NF-kB2 mutant. Microarray analysis, verified at the RNA and protein level identified new downstream targets and confirmed established regulatory networks. 201 genes were significantly changed, with 126 being upregulated and 75 downregulated. Pathway analysis uncovered both known and unknown interactions between factors important in the development of human B cell lymphomas and multiple myeloma, including cyclins D1 and D2, TRAF1, CD27, BIRC5/survivin, IL-15 and IL-10. Critical roles for STAT3 and TNF receptors are highlighted. Six target genes of STAT3 were identified: cyclins D1and D2, IL-10, survivin, IL-21 and Blimp1. Interfering with STAT3 signaling induced apoptosis in multiple myeloma cell lines. Novel pathways for NF-kB2 are proposed that involve IL-10 and other genes in the differentiation of plasma cells, evasion of apoptosis and proliferation. These pathways were verified with publically available human microarrays. Several treatment strategies based on these findings are discussed.
Publication Title
NF-κB2 mutation targets survival, proliferation and differentiation pathways in the pathogenesis of plasma cell tumors.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 3 Downloadable Samples
- Illumina HiSeq 2000
Description
Gene splicing requires three basal genetic elements; the 3’ and 5’ splice sites and the branchpoint to which the 5’ intron termini is ligated to form a closed lariat during the splicing reaction. The 5’ and 3’ splice sites that define exon boundaries have been widely identified, revealing pervasive transcription and splicing of human genes. However, the locations of the third requisite element, the branchpoint, are still largely unknown. Here we employ two complementary approaches, targeted RNA sequencing and exoribonuclease digestion, to distil sequenced reads that traverse the lariat junction and, via non-conventional alignment, locate human branchpoint nucleotides. Alignments identify 88,748 branchpoints that correspond to 20% of known introns, with 76% supported by diagnostic sequence mismatch errors. This affords a first genome-wide analysis of branchpoints, describing their distribution, selection, and the existence of a diverse array of overlapping sequence motifs with distinct usage, evolutionary histories, and co-variation with distal splicing elements. The overlap of branchpoints with noncoding human genetic variation also indicates a notable contribution to disease. This annotation and analysis incorporates branchpoints into transcriptomic research and reflects a core role for this element in the regulatory code that governs gene splicing and expression. Overall design: CaptureSeq identification of branchpoint nucleotides
Publication Title
Genome-wide discovery of human splicing branchpoints.
Sample Metadata Fields
Cell line, Subject
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Increased activation of the serine-glycine biosynthetic pathway is an integral part of cancer metabolism that drives macromolecule synthesis needed for cell proliferation. Whether this pathway is under epigenetic control is unknown. Here we show that the histone H3 lysine 9 (H3K9) methyltransferase G9A is required for maintaining the pathway enzyme genes in an active state marked by H3K9 monomethylation and for the transcriptional activation of this pathway in response to serine deprivation. G9A inactivation depletes serine and its downstream metabolites, triggering cell death with autophagy in cancer cell lines of different tissue origins. Higher G9A expression, which is observed in various cancers and is associated with greater mortality in cancer patients, increases serine production and enhances the proliferation and tumorigenicity of cancer cells. These findings identify a G9A-dependent epigenetic program in the control of cancer metabolism, providing a rationale for G9A inhibition as a therapeutic strategy for cancer.
Publication Title
The histone H3 methyltransferase G9A epigenetically activates the serine-glycine synthesis pathway to sustain cancer cell survival and proliferation.
Sample Metadata Fields
Treatment
View Samples