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GSE75841
Homo sapiens
16 Downloadable Samples
Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
microRNA are aberrantly expressed in acute myeloid leukemia (AML), and clinically may have diagnostic, prognostic, and therapeutic value. We identify one such microRNA, miR-196b, is essential for MLL-AF9 leukemia initiation and maintenance. To discover how miR-196b contributes to leukemogenesis, we utilized multiple unbiased approaches that identified and functionally screened miR-196b target activity in AML. Our studies resolved how conflicting networks of miRNA-regulated targets are integrated during leukemogenesis. This work uncovered two miR-196b direct targets, the cell cycle regulator Cdkn1b (p27Kip1) and Polycomb group member Phc2, that independently cooperate with MLL-AF9 to promote leukemogenesis by regulating stem cell transcriptional programs. Finally, we found that therapeutic disruption of miR-196b direct targeting of Cdkn1b suppresses leukemogenesis.
Publication Title
miR-196b target screen reveals mechanisms maintaining leukemia stemness with therapeutic potential.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Mus musculus
- 10 Downloadable Samples
Illumina HiSeq 2500
Description
microRNA are aberrantly expressed in acute myeloid leukemia (AML), and clinically may have diagnostic, prognostic, and therapeutic value. We identify one such microRNA, miR-196b, is essential for MLL-AF9 leukemia initiation and maintenance. To discover how miR-196b contributes to leukemogenesis, we utilized multiple unbiased approaches that identified and functionally screened miR-196b target activity in AML. Our studies resolved how conflicting networks of miRNA-regulated targets are integrated during leukemogenesis. This work uncovered two miR-196b direct targets, the cell cycle regulator Cdkn1b (p27Kip1) and Polycomb group member Phc2, that independently cooperate with MLL-AF9 to promote leukemogenesis by regulating stem cell transcriptional programs. Finally, we found that therapeutic disruption of miR-196b direct targeting of Cdkn1b suppresses leukemogenesis. Overall design: To identify the gene expression changes assoicated with knockdown of Cdkn1b and knockdown of Phc2 in murine MLL-AF9 leukemia cells.
Publication Title
miR-196b target screen reveals mechanisms maintaining leukemia stemness with therapeutic potential.
Sample Metadata Fields
Specimen part, Subject
View Samples- Mus musculus
- 8 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Tumors engender an environment dominated by M2 differentiated tumor macrophages that support tumor invasion, metastases and escape from immune control. In this study, we demonstrate that following radiation therapy of tumors in mice there is an influx of tumor macrophages that polarize towards wound repair and immune suppression.
Publication Title
Expression of NF-κB p50 in tumor stroma limits the control of tumors by radiation therapy.
Sample Metadata Fields
Specimen part, Treatment, Time
View Samples- Drosophila melanogaster
- 32 Downloadable Samples
- Illumina Genome Analyzer IIx
Description
To gain insight into the molecular underpinnings of the post-mating response that depend on the germline, we independently assess the contribution of the female germline and the male germline on gene expression changes in head tissues of females using RNA-seq. Overall design: mRNA profiles of head tissues in virgin and mated (1 and 3 days post-mating) females that either have or are lacking a germline and females mated to males that either have or are lacking a germline. Samples were generated in triplicate and sequenced on an Illumina Genome Analyzer IIx.
Publication Title
The <i>Drosophila</i> Post-mating Response: Gene Expression and Behavioral Changes Reveal Perdurance and Variation in Cross-Tissue Interactions.
Sample Metadata Fields
Sex, Age, Subject
View Samples- Mus musculus
- 18 Downloadable Samples
- Illumina HiSeq 2000
Description
Blood-stage malaria initiates both innate and adaptive immune responses, inclusive a strong activation of the mononuclear phagocyte network. Here we show that Plasmodium infection results in a transient loss of embryonically established tissue-resident macrophages in spleen, liver and lungs, much before the peak of parasitemia. During acute blood-stage malaria, fate mapping analysis revealed that inflammatory monocytes contribute to the repopulation of the emptied niches of splenic red pulp macrophages and hepatic Kupffer cells, while lung alveolar macrophages refill their niche mainly through self-renewal. Interestingly, the local microenvironment of spleen and liver can “imprint” the molecular characteristics of fetal-derived macrophages in new immigrants from bone marrow including almost identical gene expression profiles and turnover kinetics. Overall design: Mice were infected with parasitized P. yoelii erythrocytes. Organ samples were collected in triplicates from uninfected mice and from mice infected 35 days before and after parasite clearance.
Publication Title
Organ-Specific Fate, Recruitment, and Refilling Dynamics of Tissue-Resident Macrophages during Blood-Stage Malaria.
Sample Metadata Fields
Specimen part, Subject
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
We used gene expression microarrays to identify genes whose expression was influenced differently by TNFa in Fancc-deficient mice compared to wild type (WT) mice. To identify genes whose expression was directly or indirectly influenced by Fancc, we looked in particular for genes either suppressed or induced by TNF in WT cells that were not affected by TNF in Fancc-deficient cells.
Publication Title
FANCL ubiquitinates β-catenin and enhances its nuclear function.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 2 Downloadable Samples
- IlluminaHiSeq2500
Description
The inflammatory gene response requires activation of the protein kinase TAK1, but it is currently unknown how TAK1-derived signals coordinate transcriptional programs in the genome. We determined the genome-wide binding of the TAK1-controlled NF-?B subunit p65 in relation to active enhancers and promoters of transcribed genes by ChIP-seq experiments. Out of 35,000 active enhancer regions, 410 H3K4me1-positive enhancers show interleukin (IL)-1-induced H3K27ac and p65 binding. Inhibition of TAK1, IKK2 or depletion of p65 blocked inducible enhancer activation and gene expression. As exemplified by the CXC chemokine cluster located on chromosome 4, the TAK1-p65 pathway also regulates the recruitment kinetics of the histone acetyltransferase CBP, of NF-?B p50 and of AP-1 transcription factors to both, promoters and enhancers. This study provides a high resolution view of epigenetic changes occurring during the IL-1 response and allows the first genome-wide identification of a novel class of inducible p65 NF-?B-dependent enhancers in epithelial cells. Overall design: RNA-seq of KB cells either untreated or treated with IL-1 alpha
Publication Title
The Activation of IL-1-Induced Enhancers Depends on TAK1 Kinase Activity and NF-κB p65.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 30 Downloadable Samples
- Illumina MouseWG-6 v2.0 R2 expression beadchip
Description
Following exposure to vaccines, antigen-specific CD8+ T-cell responses develop as long-term memory pools. Novel vaccine strategies based on adenoviral vectors, e.g. those developed for HCV, are able to induce and sustain substantial CD8+ T-cell populations. How such populations evolve following vaccination remains to be defined at a transcriptional level. We addressed the transcriptional regulation of divergent CD8+ T-cell memory pools induced by an adenoviral vector encoding a model antigen (beta-galactosidase). We observe transcriptional profiles that mimic those following infection with persistent pathogens, murine and human cytomegalovirus (CMV). Key transcriptional hallmarks include up-regulation of homing receptors, and anti-apoptotic pathways, driven by conserved networks of transcription factors, including T-bet (TBX21). In humans, a novel adenovirus vaccine induced similar CMV-like phenotypes and underlying transcription factor regulation. These data clarify the core features of CD8+ T-cell memory following vaccination with adenovirus vectors and indicate a conserved pathway for memory development shared with persistent herpesviruses.
Publication Title
Adenoviral Vector Vaccination Induces a Conserved Program of CD8(+) T Cell Memory Differentiation in Mouse and Man.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 16 Downloadable Samples
- IlluminaHiSeq2000
Description
Induced pluripotent stem cell (iPSC)-derived cortical neurons present a powerful new model of neurological disease. Previous work has established that differentiation protocols produce cortical neurons but little has been done to characterise these at cellular resolution. In particular, it is unclear to what extent in vitro two-dimensional, relatively disordered culture conditions recapitulate the development of in vivo cortical layer identity. Single cell multiplex RT-qPCR was used to interrogate the expression of genes previously implicated in cortical layer or phenotypic identity in individual cells. Unexpectedly, 22.7% of neurons analysed frequently co-expressed canonical fetal deep and upper cortical layer markers, and this co-expression was also present at the level of translated protein. By comparing our results to available single cell RNA-seq data from human fetal and adult brain, we observed that this co-expression of layer markers was also seen in primary tissue. These results suggest that establishing neuronal layer identity in iPSC-derived or primary cortical neurons using canonical marker genes transcripts is unlikely to be informative. Overall design: Single cell RNA-seq of 16 iPSC-derived cortical neurons. This dataset was used for normalization purposes for GSE67835.
Publication Title
Assessing similarity to primary tissue and cortical layer identity in induced pluripotent stem cell-derived cortical neurons through single-cell transcriptomics.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 3 Downloadable Samples
- Illumina MouseWG-6 v2.0 expression beadchip
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Identification of cDC1- and cDC2-committed DC progenitors reveals early lineage priming at the common DC progenitor stage in the bone marrow.
Sample Metadata Fields
Sex
View Samples