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SRP097735
Homo sapiens
79 Downloadable Samples
Illumina HiSeq 2000
Description
Background: Neuroblastoma is the most common extracranial solid tumor in childhood. The vast majority of stage M patients present with disseminated tumor cells (DTCs) in the bone marrow (BM). Although these cells represent a major obstacle in the treatment of neuroblastoma patients, their transcriptomic profile was not intensively analyzed so far. Results: RNA-Seq of stage M primary tumors, enriched BM-derived DTCs and the corresponding non-tumor mononuclear cells (MNCs) revealed that DTCs largely retained the gene expression signature of tumors. However, we identified 322 genes that were differentially expressed (q < 0.001, |log2FC|>2). Particularly genes encoded by mitochondrial DNA were highly up-regulated in DTCs, whereas e.g. genes involved in angiogenesis were down-regulated. Furthermore, 224 genes were highly expressed in DTCs and only slightly, if at all, in MNCs (q < 8x10-75 log2FC > 6). Interestingly, we found that the gene expression profiles of diagnostic DTCs largely resembled those of relapse DTCs with only 113 differentially expressed genes under relaxed cut-offs (q < 0.01, |log2FC| > 0.5). Notably, relapse DTCs showed a positional enrichment of 31 down-regulated genes encoded by chromosome 19, including five tumor suppressor genes (SIRT6, PUMA, STK11, CADM4 and GLTSCR2). Conclusion: This first RNA-Seq analysis of DTCs from neuroblastoma patients revealed their unique expression profile in comparison to the corresponding MNCs and tumor samples, and, interestingly, also expression differences between diagnostic and relapse DTCs preferentially affecting chromosome 19. As these alterations might be associated with treatment failure and disease relapse, they should be considered for further functional studies. Overall design: Tumor (n=16), bone marrow-derived disseminated tumor cells (n=42) and corresponding bone marrow-derived non-tumor cells (n=28) of stage M neuroblastoma patients were used for RNA-Seq
Publication Title
Neuroblastoma cells undergo transcriptomic alterations upon dissemination into the bone marrow and subsequent tumor progression.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 24 Downloadable Samples
- Illumina HiSeq 2000
Description
The remarkable feature of Schwann cells (SCs) to transform into a repair phenotype turned the spotlight on this powerful cell type. SCs provide the regenerative environment for axonal re-growth after peripheral nerve injury (PNI) and play a vital role in differentiation of neuroblastic tumors into a benign subtype of neuroblastoma, a tumor originating from neural crest-derived neuroblasts. Hence, understanding their mode-of-action is of utmost interest for new approaches in regenerative medicine, but also for neuroblastoma therapy. However, literature on human SCs is scarce and it is unknown to which extent human SC cultures reflect the SC repair phenotype developing after PNI in patients. We performed high-resolution proteome profiling and RNA-sequencing on highly enriched human SC and fibroblast cultures, control and ex vivo degenerated nerve explants to identify novel molecules and functional processes active in repair SCs. In fact, we found cultured SCs and degenerated nerves to share a similar repair SC-associated expression signature, including the upregulation of JUN, as well as two prominent functions, i.e., myelin debris clearance and antigen presentation via MHCII. In addition to myelin degradation, cultured SCs were capable of actively taking up cell-extrinsic components in functional phagocytosis and co-cultivation assays. Moreover, in cultured SCs and degenerated nerve tissue MHCII was upregulated at the cellular level along with high expression of chemoattractants and co-inhibitory rather than -stimulatory molecules. These results demonstrate human SC cultures to execute an inherent program of nerve repair and support two novel repair SC functions, debris clearance via phagocytosis-related mechanisms and type II immune-regulation. Overall design: mRNA of 27 samples were sequenced (50bp, single end) and analyzed. Biological replicates were performed.
Publication Title
Proteomics and transcriptomics of peripheral nerve tissue and cells unravel new aspects of the human Schwann cell repair phenotype.
Sample Metadata Fields
Subject
View Samples- Homo sapiens
- 48 Downloadable Samples
Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
G protein alpha q and 11 are mutated in 80% of uveal melanoma. We observed that treatment with the BRD4 inhibitor JQ1 resulted in different phenotypic responses in G-protein mutant uveal melanoma cell lines and wild type uveal melanoma cell lines.
Publication Title
BRD4-targeted therapy induces Myc-independent cytotoxicity in Gnaq/11-mutatant uveal melanoma cells.
Sample Metadata Fields
Cell line, Treatment
View Samples- Caenorhabditis elegans
- 12 Downloadable Samples
- Affymetrix C. elegans Genome Array (celegans)
Description
Gene expression in early animal embryogenesis is in large part controlled post-transcriptionally. Maternally-contributed microRNAs may therefore play important roles in early development. We have elucidated a major biological role of the nematode mir-35 family of maternally-contributed, essential microRNAs. We show that this microRNA family regulates the sex determination pathway at multiple levels, acting both upstream and downstream of her-1 to prevent aberrantly activated male developmental programs in hermaphrodite embryos. The predicted target genes that act downstream of the mir-35 family in this process, sup-26 and nhl-2, both encode RNA binding proteins, thus delineating a previously unknown post-transcriptional regulatory subnetwork within the well-studied sex determination pathway of C. elegans. Repression of nhl-2 by the mir-35 family is not only required for proper sex determination but also for viability, showing that a single microRNA target site can be essential. Since sex determination in C. elegans requires zygotic gene expression to read the sex chromosome karyotype, early embryos must remain gender-nave; our findings show that the mir-35 family microRNAs act in the early embryo to function as a developmental timer that preserves navet and prevents premature deleterious developmental decisions.
Publication Title
A microRNA family exerts maternal control on sex determination in <i>C. elegans</i>.
Sample Metadata Fields
Specimen part
View Samples- Caenorhabditis elegans
- 6 Downloadable Samples
- Affymetrix C. elegans Genome Array (celegans)
Description
Gene expression in early animal embryogenesis is in large part controlled post-transcriptionally. Maternally-contributed microRNAs may therefore play important roles in early development. We have elucidated a major biological role of the nematode mir-35 family of maternally-contributed, essential microRNAs. We show that this microRNA family regulates the sex determination pathway at multiple levels, acting both upstream and downstream of her-1 to prevent aberrantly activated male developmental programs in hermaphrodite embryos. The predicted target genes that act downstream of the mir-35 family in this process, sup-26 and nhl-2, both encode RNA binding proteins, thus delineating a previously unknown post-transcriptional regulatory subnetwork within the well-studied sex determination pathway of C. elegans. Repression of nhl-2 by the mir-35 family is not only required for proper sex determination but also for viability, showing that a single microRNA target site can be essential. Since sex determination in C. elegans requires zygotic gene expression to read the sex chromosome karyotype, early embryos must remain gender-nave; our findings show that the mir-35 family microRNAs act in the early embryo to function as a developmental timer that preserves navet and prevents premature deleterious developmental decisions.
Publication Title
A microRNA family exerts maternal control on sex determination in <i>C. elegans</i>.
Sample Metadata Fields
Specimen part
View Samples- Caenorhabditis elegans
- 4 Downloadable Samples
Description
Gene expression in early animal embryogenesis is in large part controlled post-transcriptionally. Maternally-contributed microRNAs may therefore play important roles in early development. We have elucidated a major biological role of the nematode mir-35 family of maternally-contributed, essential microRNAs. We show that this microRNA family regulates the sex determination pathway at multiple levels, acting both upstream and downstream of her-1 to prevent aberrantly activated male developmental programs in hermaphrodite embryos. The predicted target genes that act downstream of the mir-35 family in this process, sup-26 and nhl-2, both encode RNA binding proteins, thus delineating a previously unknown post-transcriptional regulatory subnetwork within the well-studied sex determination pathway of C. elegans. Repression of nhl-2 by the mir-35 family is not only required for proper sex determination but also for viability, showing that a single microRNA target site can be essential. Since sex determination in C. elegans requires zygotic gene expression to read the sex chromosome karyotype, early embryos must remain gender-nave; our findings show that the mir-35 family microRNAs act in the early embryo to function as a developmental timer that preserves navet and prevents premature deleterious developmental decisions.
Publication Title
A microRNA family exerts maternal control on sex determination in <i>C. elegans</i>.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 27 Downloadable Samples
- Affymetrix Human Exon 1.0 ST Array [transcript (gene) version (huex10st)
Description
Sjgren's syndrome is an autoimmune disease manifesting primarily as dryness of eyes and mouth. In this study, we compared gene expression in PBMCs between age- and gender-matched patients with Sjgren's syndrome (diagnosed by ACR criteria) and healthy controls. Cells were collected in heparinized tubes and PBMCs were prepared using Ficoll.
Publication Title
Expression of the immune regulator tripartite-motif 21 is controlled by IFN regulatory factors.
Sample Metadata Fields
Specimen part, Disease
View Samples- Homo sapiens
- 1 Downloadable Sample
- Affymetrix Human Gene 2.0 ST Array (hugene20st)
Description
Epstein-Barr virus is associated with several human malignancies, including Burkitt Lymnphoma. The virus encodes more than 40 microRNAs, which participate in its possible pathogenetic role.
Publication Title
Molecular signature of Epstein Barr virus-positive Burkitt lymphoma and post-transplant lymphoproliferative disorder suggest different roles for Epstein Barr virus.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 4 Downloadable Samples
- NextSeq 500
Description
We performed RNA-seq on human embryonic stem cells raised in an established condition to produce 95% Nkx2.1 cells, with and without withdrawal of Wnt-agonist CHIR99021 or addition of Wnt-inhibitor IWP2 Overall design: Human lung progenitors were derived from RUES2 as described in Huang et al 2014, Huang et al 2015. Wnt agonist withdrawal or addition of Wnt inhibitor was done at day 12, with cell harvest for RNA-seq at day 12 (control) and day 15 (control and treatment)
Publication Title
β-Catenin maintains lung epithelial progenitors after lung specification.
Sample Metadata Fields
Specimen part, Treatment, Subject, Time
View Samples- Mus musculus
- 5 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Regulation of mRNA stability by RNA-protein interactions contributes significantly to quantitative aspects of gene expression. We have identified potential mRNA targets of the AU-rich element binding protein AUF1. Myc-tagged AUF1 p42 was induced in mouse NIH-3T3 cells and RNA-protein complexes isolated using anti-myc tag antibody beads. Bound mRNAs were analyzed with Affymetrix microarrays. We have identified 508 potential target mRNAs that were at least 3-fold enriched compared to control cells without myc-AUF1. 22.3% of the enriched mRNAs had an AU-rich cluster in the ARED Organism database, against 16.3% of non-enriched control mRNAs. The enrichment towards AU-rich elements was also visible by AREScore with an average value of 5.2 in the enriched mRNAs versus 4.2 in the control group. Yet, many mRNAs were enriched without a high ARE score suggesting that AUF1 has a broader binding spectrum than standard AUUUA repeats. AUF1 did not preferentially bind to unstable mRNAs. Still, some enriched mRNAs were highly unstable, as those of TNFSF11 (known as RANKL), KLF10, HES1, CCNT2, SMAD6, and BCL6. We have mapped some of the instability determinants. HES1 mRNA appeared to have a coding region determinant. Detailed analysis of the RANKL and BCL6 3UTR revealed for both that full instability required two elements, which are conserved in evolution. In RANKL mRNA both elements are AU-rich and separated by 30 bases, while in BCL6 mRNA one is AU-rich and 60 bases from a non AU-rich element that potentially forms a stem-loop structure.
Publication Title
Short-lived AUF1 p42-binding mRNAs of RANKL and BCL6 have two distinct instability elements each.
Sample Metadata Fields
Cell line
View Samples