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Homo sapiens
9 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Neuroblastoma is a pediatric tumor of the peripheral sympathetic nervous system with a highly variable prognosis. Activation of the PI3K/AKT pathway in neuroblastoma is correlated with poor patient prognosis, but the precise downstream effectors mediating this effect have not been determined. Here, we identify the forkhead transcription factor FOXO3a as a key target of the PI3K/AKT pathway in neuroblastoma. FOXO3a expression was elevated in low stage neuroblastoma tumors and normal embryonal neuroblasts, but reduced in late stage neuroblastoma. Inactivation of FOXO3a by AKT was essential for neuroblastoma cell survival. Treatment of neuroblastoma cells with the dual PI3K/mTOR inhibitor PI-103 activated FOXO3a and triggered apoptosis. This effect was rescued by FOXO3a silencing. Conversely, apoptosis induced by PI-103 or the AKT inhibitor MK-2206 was potentiated by FOXO3a overexpression. Further, levels of total or phosphorylated FOXO3a correlated closely with apoptotic sensitivity to MK-2206. In clinical specimens, there was an inverse relationship between gene expression signatures regulated by PI3K signaling and FOXO3a transcriptional activity. Moreover, high PI3K activity and low FOXO3a activity were each associated with an extremely poor prognosis. Our work indicates that expression of FOXO3a and its targets offer useful prognostic markers as well as biomarkers for PI3K/AKT inhibitor efficacy in neuroblastoma.
Publication Title
FOXO3a is a major target of inactivation by PI3K/AKT signaling in aggressive neuroblastoma.
Sample Metadata Fields
Specimen part, Cell line, Treatment
View Samples- Homo sapiens
- 38 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
A NOTCH feed-forward loop drives reprogramming from adrenergic to mesenchymal state in neuroblastoma.
Sample Metadata Fields
Specimen part, Cell line, Time
View Samples- Homo sapiens
- 86 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
mRNA profiles of thousands of human tumors are available, but methods to deduce oncogenic signaling networks from these data lag behind. It is especially challenging to identify main-regulatory routes, and to generalize conclusions obtained from experimental models. We designed the bioinformatic platform R2 in parallel with a wet-lab approach of neuroblastoma. Here we demonstrate how R2 facilitates an integrated analysis of our neuroblastoma data. Analysis of the MYCN pathway suggested important regulatory connections to the polyamine synthesis route, the Notch pathway and the BMP/TGF pathway. A network of genes emerged connecting major oncogenes in neuroblastoma. Genes in the network carried strong prognostic values and were essential for tumor cell survival.
Publication Title
Sequencing of neuroblastoma identifies chromothripsis and defects in neuritogenesis genes.
Sample Metadata Fields
Specimen part
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GSE76320- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Genome 430A 2.0 Array (mouse430a2)
Description
Depletion of Rad21 in murine bone marrow leads to enhanced self-renewal in vitro
Publication Title
The cohesin subunit Rad21 is a negative regulator of hematopoietic self-renewal through epigenetic repression of Hoxa7 and Hoxa9.
Sample Metadata Fields
Specimen part
View Samples- Caenorhabditis elegans
- 12 Downloadable Samples
Illumina HiSeq 4000
Description
Worms that inherited the sperm genome lacking the repressive mark H3K27me3 (K27me3 M+P-) misexpress genes in their germlines when compared to genetically identitical worms that inherited the sperm genome with H3K27me3 (K27me3 M+P+). Overall design: Transcriptome profiles of hermaphrodite germlines from hybrid worms that inherited the sperm genome with H3K27me3 (4 replicates of K27me3 M+P+) vs without H3K27me3 (4 replicates K27me3 M+P-) to compare to 4 replicates of 'wildtype'.
Publication Title
Sperm-inherited H3K27me3 impacts offspring transcription and development in C. elegans.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Caenorhabditis elegans
- 6 Downloadable Samples
- Illumina HiSeq 2000
Description
The germ lineage is considered to be immortal. In the quest to extend lifespan, a possible strategy is to drive germline traits in somatic cells, to try to confer some of the germ lineage’s immortality on the somatic body. Notably, a study in C. elegans suggested that expression of germline genes in the somatic cells of long-lived daf-2 mutants confers some of daf-2’s longevity. Specifically, mRNAs encoding components of C. elegans germ granules (P granules) were up-regulated in daf-2 mutant worms, and knock-down of individual P-granule and other germline genes in daf-2 young adults modestly reduced their lifespan. We investigated the contribution of a germline program to daf-2’s long lifespan, and also tested if other mutants known to express germline genes in their somatic cells are long-lived. Our key findings are: 1) We could not detect P-granule proteins in the somatic cells of daf-2 mutants by immunostaining or by expression of a P-granule transgene. 2) Whole-genome transcript profiling of animals lacking a germline revealed that germline transcripts are not up-regulated in the soma of daf-2 worms compared to the soma of control worms. 3) Simultaneous removal of multiple P-granule proteins or the entire germline program from daf-2 worms did not reduce their lifespan. 4) Several mutants that robustly express a broad spectrum of germline genes in their somatic cells are not long-lived. Taken together, our findings argue against the hypothesis that acquisition of a germ cell program in somatic cells increases lifespan and contributes to daf-2’s longevity. Overall design: Transcriptome profiles of 3 replicates of sterile daf-2; mes-1 double mutants (experimental) and 3 replicates of sterile mes-1 single mutants (control) grown at 24°C
Publication Title
Reevaluation of whether a soma-to-germ-line transformation extends lifespan in Caenorhabditis elegans.
Sample Metadata Fields
Cell line, Subject
View Samples- Homo sapiens
- 13 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Purpose: Determine if gene expression profiles in urine sediment could provide non-invasive candidate markers for painful bladder syndrome (PBS) with and/or without Hunner lesions. Materials and Methods: Fresh catheterized urine was collected and centrifuged from control (n = 5), lesion-free (n = 5), and Hunner lesion bearing (n = 3) patients. RNA was extracted from the pelleted material and quantified by gene expression microarray (Affymetrix Human Gene ST Array). Results: Three biologically likely hypotheses were tested: A) all three groups are distinct from one another; B) controls are distinct from both types of PBS patients combined, and C) Hunner lesion PBS patients are distinct from controls and non-Hunner-lesion PBS combined. For statistical parity an unlikely fourth hypothesis was included: non-Hunner-lesion PBS patients are distinct from controls and Hunner lesion PBS combined. Analyses supported selective upregulation of genes in the Hunner lesion PBS group (hypothesis C), and these were primarily associated with inflammatory function. This profile is similar to that reported in a prior microarray study of bladder biopsies in Hunner lesion PBS. Conclusions: Urine sediment gene expression from non-Hunner-lesion PBS patients lacked a clear difference from that of control subjects, while the array signatures from PBS patients with Hunner lesions showed a clear, primarily inflammatory, signature. This signature was highly similar to that seen in a prior microarray study of bladder biopsies. Thus, although sample sizes were small, this work suggests that gene expression in urine sediment may provide a non-invasive biomarker for Hunner lesion, but not non-Hunner lesion, PBS.
Publication Title
Gene expression analysis of urine sediment: evaluation for potential noninvasive markers of interstitial cystitis/bladder pain syndrome.
Sample Metadata Fields
Sex, Age, Disease, Disease stage
View Samples- Caenorhabditis elegans
- 12 Downloadable Samples
- Affymetrix C. elegans Genome Array (celegans)
Description
Here we uncover antagonistic regulation of transcript levels in the germline of Caenorhabditis elegans hermaphrodites. The histone methyltransferase MES-4 marks genes expressed in the germline with methylated Lys36 on histone H3 (H3K36me) and promotes their transcription; MES-4 also represses genes normally expressed in somatic cells and genes on the X chromosomes. The DRM complex, which includes E2F/DP and Retinoblastoma homologs, affects germline gene expression and prevents excessive repression of X-chromosome genes. Using genome-scale analyses of germline tissue, we show that common germline-expressed genes are activated by MES-4 and repressed by DRM, and that MES-4 and DRM co-bind many germline-expressed genes. Reciprocally, MES-4 represses and DRM activates a set of autosomal soma-expressed genes and overall X-chromosome gene expression. Mutations in mes-4 or the DRM subunit lin-54 oppositely skew target transcript levels and cause sterility; a double mutant restores near wild-type transcript levels and germ cell development. Together, yin-yang regulation by MES-4 and DRM ensures transcript levels appropriate for germ cell function, elicits robust but not excessive dampening of X-chromosome-wide transcription, and may poise genes for future expression changes. Our study reveals that conserved transcriptional regulators implicated in development and cancer counteract each other to fine-tune transcript dosage.
Publication Title
Opposing activities of DRM and MES-4 tune gene expression and X-chromosome repression in Caenorhabditis elegans germ cells.
Sample Metadata Fields
Sex
View Samples- Mus musculus
- 3 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Identification of all genes expressed by mouse olfactory sensory neurons; genes expressed in mature neurons, immature neurons, or both were distinguished. Independent validation of enrichment ratio values supported by statistical assessment of error rates was used to build a database of statistical probabilities of the expression of all mRNAs detected in mature neurons, immature neurons, both types of neurons (shared), and the residual population of all other cell types.
Publication Title
Genomics of mature and immature olfactory sensory neurons.
Sample Metadata Fields
Sex, Specimen part
View Samples- Glycine max
- 2 Downloadable Samples
- Illumina Genome Analyzer II
Description
Two high throughput transcript sequencing methods, Digital Gene Expression (DGE) Tag Profiling and RNA-Seq, were used to compare the transcriptional profiles in wild-type (cv. Clark standard, CS) and a mutant (cv. Clark glabrous, i.e., trichomeless or hairless, CG) soybean isoline that carries the dominant P1 allele. DGE data and RNA-Seq data were mapped to the cDNAs (Glyma models) predicted from the reference soybean genome, Williams 82. Extending the model length by 250 bp at both ends resulted in significantly more matches of authentic DGE tags indicating that many of the predicted gene models are prematurely truncated at the 5' and 3' UTRs. The genome-wide comparative study of the transcript profiles of the wild-type versus mutant line revealed a number of differentially expressed genes. One highly-expressed gene, Glyma04g35130, in wild-type soybean was of interest as it has high homology to the cotton gene GhRDL1 gene that has been identified as being involved in cotton fiber initiation and is a member of the BURP protein family. Sequence comparison of Glyma04g35130 among Williams 82 with our sequences derived from CS and CG isolines revealed various SNPs and indels including addition of one nucleotide C in the CG and insertion of ~60 bp in the third exon of CS that causes a frameshift mutation and premature truncation of peptides in both lines as compared to Williams 82. Overall design: 2 samples examined: Clark standard (wild type) and Clark glabrous (soybean hairless mutant)
Publication Title
Transcript profiling reveals expression differences in wild-type and glabrous soybean lines.
Sample Metadata Fields
Specimen part, Subject
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