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SRP062760
Mus musculus
1 Downloadable Sample
Illumina HiSeq 2500
Description
Analysis of gene expression in the distal forelimbs Overall design: RNA-Seq polyA on transcripts extracted from the dissection of three pairs of embryonnic forelimbs at E12.5
Publication Title
Nanoscale spatial organization of the HoxD gene cluster in distinct transcriptional states.
Sample Metadata Fields
Cell line, Subject
View Samples- Mus musculus
- 6 Downloadable Samples
- Illumina HiSeq 2500
Description
In this work we have analyzed the transcriptomic profiles of E13.5 mouse embryonic mammary buds. We show that Hoxd8 and Hoxd9, two gene members of the HoxD cluster, are transcribed during mammary bud development. Yet, unlike in other developmental contexts, their co-expression does not rely upon the same regulatory mechanism. Hoxd8 is regulated by the combined activity of closely located sequences and the most distant telomeric gene desert. On the other hand, Hoxd9 is controlled by an enhancer sequence also located within the telomeric gene desert, but which has no impact on Hoxd8 transcription, thus constituting an exception to the global regulations systematically observed at this locus. The latter DNA region is also involved in Hoxd gene regulation in other contexts and strongly interacts with Hoxd9 in all tissues analyzed so far as well as in other vertebrate species, indicating that its regulatory activity was already operational before the appearance of mammary glands. Within this DNA region and neighboring the CS39 limb enhancer, we further identified a short sequence conserved in therian mammals and capable of enhancer activity in the mammary buds. We propose that Hoxd gene regulation in embryonic mammary buds evolved by hijacking a preexisting regulatory landscape, which was already at work before the emergence of mammals in structures such like the limbs or the intestinal tract. Overall design: RNA-seq analysis of e13.5 mammary buds and adjacent embryonic skin
Publication Title
Control of Hoxd gene transcription in the mammary bud by hijacking a preexisting regulatory landscape.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Mus musculus
- 38 Downloadable Samples
- Illumina HiSeq 3000
Description
Colorectal cancer is treated with antibodies blocking epidermal growth factor receptor (EGF-R) but therapeutic success is limited. EGF-R is stimulated by soluble ligands, which are derived from transmembrane precursors by ADAM17-mediated proteolytic cleavage. In mouse intestinal cancer models in the absence of ADAM17, tumorigenesis was almost completely inhibited and the few remaining tumors were of low grade dysplasia. RNA-Seq analysis demonstrated downregulation of STAT3 and Wnt pathway components. Since EGF-R on myeloid cells, but not on intestinal epithelial cells is required for intestinal cancer and IL-6 is induced via EGF-R stimulation, we analyzed the role of IL-6 signaling. Tumor formation was equally inhibited in IL-6 -/- and sgp130Fc transgenic mice, in which only trans-signaling via soluble IL-6R is abrogated. ADAM17 is needed for EGF-R-mediated induction of IL-6 synthesis, which via IL-6 trans-signaling induces ß-catenin dependent tumorigenesis. Our data reveal the possibility of a novel strategy for treatment of colorectal cancer, which could circumvent intrinsic and acquired resistance to EGF-R blockade. Overall design: RNA sequencing of tumor tissue and surrounding unaffected tissue of Apc Min/+ and Apc Min/+ ::ADAM17 ex/ex
Publication Title
ADAM17 is required for EGF-R-induced intestinal tumors via IL-6 trans-signaling.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Mus musculus
- 10 Downloadable Samples
Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
ZEB2 is a multi-zinc-finger transcription factor known to play a significant role in early neurogenesis and in EMT-dependent tumor metastasis. While the function of ZEB2 in T lymphocytes is unknown, activity of the closely related family member ZEB1 has been implicated in lymphocyte development. Here, we find that ZEB2 expression is upregulated by activated T cells, specifically in the KLRG1hi effector CD8+ T cell subset. Loss of ZEB2 expression results in a significant loss of antigen-specific CD8+ T cells following primary and secondary infection with a severe impairment in the generation of the KLRG1hi effector-memory cell population. We show that ZEB2, which can bind DNA at tandem, consensus E-box sites, regulates gene expression of several E-protein targets and may directly repress CD127 and IL-2 in CD8+ T cells responding to infection. Furthermore, we find that T-bet binds to highly conserved T-box-sites in the ZEB2 gene and that T-bet and ZEB2 regulate similar gene-expression programs in effector T cells, suggesting that T-bet acts upstream and through regulation of ZEB2. Taken together, we place ZEB2 in a larger transcriptional network that is responsible for the balance between terminal differentiation and formation of memory CD8+ T cells.
Publication Title
Transcriptional repressor ZEB2 promotes terminal differentiation of CD8+ effector and memory T cell populations during infection.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Homo sapiens
- 24 Downloadable Samples
- IlluminaHiSeq2000
Description
This experiment aims to identify the biological pathways and diseases associated with the cytokine Interleukin 13 (IL-13) using gene expression measured in peripheral blood mononuclear cells (PBMCs). Overall design: The experiment comprised of samples obtained from 3 healthy donors. The expression profiles of in vitro IL-13 stimulation were generated using RNA-seq technology for 3 PBMC samples at 24 hours. The transcriptional profiles of PBMCs without IL-13 stimulation were also generated to be used as controls. An IL-13R-alpha antagonist (Redpath et al. Biochemical Journal, 2013) was introduced into IL-13 stimulated PBMCs and the gene expression levels after 24h were profiled to examine the neutralization of IL-13 signaling by the antagonist.
Publication Title
Combining multiple tools outperforms individual methods in gene set enrichment analyses.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 9 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Reduced oxygen availability during embryogenesis leads to intra-uterine growth restriction (IUGR), increasing the risk for hypertension, cardiovascular and chronic kidney disease (CKD) in adults. Although this association has long been recognized, underlying mechanisms still require extensive research.
Publication Title
Fetuin-A is a HIF target that safeguards tissue integrity during hypoxic stress.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Homo sapiens
- 32 Downloadable Samples
- IlluminaHiSeq2000
Description
Background: Transcription control of mitochondrial metabolism is essential for cellular function. A better understanding of this process will aid the elucidation of mitochondrial disorders, in particular of the many genetically unsolved cases of oxidative phosphorylation (OXPHOS) deficiency. Yet, to date only few studies have investigated nuclear gene regulation in the context of OXPHOS deficiency. In this study, we combined RNA sequencing of human complex I-deficient patient cells across 32 conditions of perturbed mitochondrial metabolism, with a comprehensive analysis of gene expression patterns, co-expression calculations and transcription factor binding sites. Results: Our analysis shows that OXPHOS genes have a significantly higher co-expression with each other than with other genes, including mitochondrial genes. We found no evidence for complex-specific mRNA expression regulation in the tested cell types and conditions: subunits of different OXPHOS complexes are similarly (co-)expressed and regulated by a common set of transcription factors. However, we did observe significant differences between the expression of OXPHOS complex subunits compared to assembly factors, suggesting divergent transcription programs. Furthermore, complex I co-expression calculations identified 684 genes with a likely role in OXPHOS biogenesis and function. Analysis of evolutionarily conserved transcription factor binding sites in the promoters of these genes revealed almost all known OXPHOS regulators (including GABP, NRF1/2, SP1, YY1, E-box factors) and a set of six yet uncharacterized candidate transcription factors (ELK1, KLF7, SP4, EHF, ZNF143, and EL2). Conclusions: OXPHOS genes share an expression program distinct from other mitochondrial genes, indicative of targeted regulation of this mitochondrial sub-process. Within the subset of OXPHOS genes we established a difference in expression between subunits and assembly factors. Most transcription regulators of genes that co-express with complex I are well-established factors for OXPHOS biogenesis. For the remaining six factors we here suggest for the first time a link with transcription regulation in OXPHOS deficiency. Overall design: RNA-SEQ of whole cell RNA in 2 control and 2 complex I deficient patient fibroblast cell lines treated with 4 compounds in duplicate, resulting in a total of 2x2x4x2=32 samples
Publication Title
Transcriptome analysis of complex I-deficient patients reveals distinct expression programs for subunits and assembly factors of the oxidative phosphorylation system.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 18 Downloadable Samples
- Affymetrix Mouse Expression 430B Array (moe430b)
Description
BRCA1 nestin CRE conditional knockout cortrices of P7 animals were compared to wildtype littermates to characterize the mutant phenotype.
Publication Title
BRCA1 tumour suppression occurs via heterochromatin-mediated silencing.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 14 Downloadable Samples
- Affymetrix Murine Genome U74A Version 2 Array (mgu74av2)
Description
SUMMARY
Publication Title
Loss of patched and disruption of granule cell development in a pre-neoplastic stage of medulloblastoma.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 11 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Little is known about the early transcriptional events in innate immune signaling in immature and tolerogenic monocyte-derived dendritic cells (DCs), the professional antigen-presenting cells of our immune system. TLR ligands usually induce a proinflammatory transcriptional response, whereas IL10 and/or dexamethasone induce a more tolerogenic phenotype.
Publication Title
MicroRNA genes preferentially expressed in dendritic cells contain sites for conserved transcription factor binding motifs in their promoters.
Sample Metadata Fields
Specimen part
View Samples