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GSE81248
Homo sapiens
12 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The innate immune system is vital to rapidly responding to pathogens and Toll-like receptors (TLRs) are a critical component of this response. Nanovesicular exosomes play a role in immunity, but to date their exact contribution to the dissemination of the TLR response is unknown. To understand the effect of exosomal cargo released from locally stimulated cells on distal cell expression, we collected exosomes from local ovarian adenocarcinoma (HEY) cells that were either unstimulated (control-exosomes), stimulated with pIC (pIC-exosomes), or lipopolysaccharide (LPS-exosomes) for 48 hours. The three groups of exosomes were added to nave (distal) cells and the gene expression profiles were compared between local TLR stimulation (for 6 hours) and distal stimulation mediated by exosomes at the 48-hour time point
Publication Title
TLR-exosomes exhibit distinct kinetics and effector function.
Sample Metadata Fields
Specimen part, Cell line, Treatment
View Samples- Mus musculus
- 1 Downloadable Sample
Illumina Genome Analyzer II
Description
We employed miRNA-seq to profile all miRNAs from a pure population of hand-dissected polyploid TGCs from embryonic day 9.5. These data set of polyploid-specific TGCs microRNAs will provide insights into TGCs differentiation and endoreplication. Overall design: TGCs were micro-dissected from day E9.5 nine implantation sites from C57BL/J6 mice. The portion of the TGCs in direct contact with the spongiotrophoblast layer and the labyrinth layer were manually removed to avoid collecting any polyploid cells from the former or multi-nucleated syncytiotrophoblast cells from the latter.
Publication Title
Fundamental differences in endoreplication in mammals and Drosophila revealed by analysis of endocycling and endomitotic cells.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Mus musculus
- 1 Downloadable Sample
- Illumina Genome Analyzer II
Description
We employed RNA-seq to transcriptionally profile a pure population of hand-dissected polyploid TGCs from embryonic day 9.5. These data provide a set of polyploid-specific TGCs transcripts that will aid in the understanding of TGCs differentiation and endoreplication. Overall design: TGCs were micro-dissected from day E9.5 nine implantation sites from C57BL/6J mice. The portion of the TGCs in direct contact with the spongiotrophoblast layer and the labyrinth layer were manually removed to avoid collecting any polyploid cells from the former or multi-nucleated syncytiotrophoblast cells from the latter.
Publication Title
Fundamental differences in endoreplication in mammals and Drosophila revealed by analysis of endocycling and endomitotic cells.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Cell isolation induces fate changes of bone marrow mesenchymal cells leading to loss or alternatively to acquisition of new differentiation potentials.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Mesenchymal populations include a fraction of cells exhibiting multipotency as well as others with limited differentiation range. It has been assumed that the mesenchymal cellular cascade is topped by a multipotent cell, which gives rise to progeny with diminishing differentiation potentials. Here we show that cultured mesenchymal cells, a priori exhibiting a limited differentiation potential, may gain new capacities and become multipotent following single cell isolation. These fate changes were accompanied by up-regulation of differentiation promoting genes, many of which also became H4K20me1 methylated. Early events in the process included TGF and Wnt modulation, and down-regulation of hypoxia signaling. Indeed, hypoxic conditions inhibited the observed cell changes. Overall, cell isolation from neighboring partners caused major molecular changes and particularly, a newly established epigenetic state. It is suggested that MSCs behave non-deterministically and non-hierarchically and should therefore be defined primarily by their capacity to undergo fate changes triggered by environmental cues.
Publication Title
Cell isolation induces fate changes of bone marrow mesenchymal cells leading to loss or alternatively to acquisition of new differentiation potentials.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Mesenchymal populations include a fraction of cells exhibiting multipotency as well as others with limited differentiation range. It has been assumed that the mesenchymal cellular cascade is topped by a multipotent cell, which gives rise to progeny with diminishing differentiation potentials. Here we show that cultured mesenchymal cells, a priori exhibiting a limited differentiation potential, may gain new capacities and become multipotent following single cell isolation. These fate changes were accompanied by up-regulation of differentiation promoting genes, many of which also became H4K20me1 methylated. Early events in the process included TGF and Wnt modulation, and down-regulation of hypoxia signaling. Indeed, hypoxic conditions inhibited the observed cell changes. Overall, cell isolation from neighboring partners caused major molecular changes and particularly, a newly established epigenetic state. It is suggested that MSCs behave non-deterministically and non-hierarchically and should therefore be defined primarily by their capacity to undergo fate changes triggered by environmental cues.
Publication Title
Cell isolation induces fate changes of bone marrow mesenchymal cells leading to loss or alternatively to acquisition of new differentiation potentials.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Mesenchymal stromal cells (MSCs) are used extensively in clinical trials; however, the potential for malignant transformation of MSCs has been raised. We examined the genomic stability versus the tumor forming capacity of multiple mouse MSCs. Murine MSCs have been shown to be less stable and more prone to malignant transformation than their human counterparts. A large series of independently isolated MSC populations exhibited low tumorigenic potential under syngeneic conditions, which increased in immune-compromised animals. Unexpectedly, higher ploidy correlated with reduced tumor forming capacity. Furthermore, in both cultured MSCs and primary hepatocytes, polyploidization was associated with a dramatic decrease in the expression of the long non-coding RNA H19. Direct knockdown of H19 expression in diploid cells resulted in acquisition of polyploid cell traits. Moreover, artificial tetraploidization of diploid cancer cells led to a reduction of H19 levels, as well as to an attenuation of the tumorigenic potential. Polyploidy might therefore serve as a protective mechanism aimed at reducing malignant transformation through the involvement of the H19 regulatory long non-coding RNA.
Publication Title
Polyploidization of murine mesenchymal cells is associated with suppression of the long noncoding RNA H19 and reduced tumorigenicity.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 8 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
The ability of transcriptional regulators to drive lineage conversion of somatic cells offers great potential for the treatment of human disease. While current research in this field is focused on the generation of induced pluripotent stem cells or direct lineage transdifferentiation, less attention has been paid to the possibility of reprogramming cells to produce cytokines, growth factors and hormones. To explore the concept of switching on specific target genes in heterologous cells, we developed a model system to screen candidate factors for their ability to activate the archetypal megakaryocyte-specific chemokine platelet factor 4 (PF4) in fibroblasts. We found that co-expression of the transcriptional regulators GATA1 and FLI1 resulted in a significant increase in levels of PF4, which became magnified over time. We also determined that inclusion of a third factor, TAL1, further enhanced upregulation of PF4 expression. Our study therefore identified of TAL1 as an important component in the combination of transcriptional regulators that contribute to megakaryocyte programming, and demonstrated that such combinations can be used to produce potentially beneficial chemokines in readily available heterologous cell types.
Publication Title
Partial reprogramming of heterologous cells by defined factors to generate megakaryocyte lineage-restricted biomolecules.
Sample Metadata Fields
Time
View Samples- Mus musculus
- 27 Downloadable Samples
- Illumina HiSeq 2000
Description
In prior work we developed an optogenetic system for delivering highly precise, time-varying inputs to Ras, termed OptoSOS (Toettcher et al., 2013). This system relies on a membrane-targeted photoswitchable protein (Phy-CAAX) and a cytoplasmic Ras activator (PIF-SOScat) whose localization to the membrane can be controlled with light. In this system, Phy/PIF heterodimerization can be triggered on and off by exposure to 650 and 750 nm light, respectively. We found that this system could be used to deliver highly precise levels and dynamics of Ras/Erk signaling both in vitro and in vivo. Here, we aimed to globally assess the transcriptional response to light-activated Ras and compare it to that induced by growth factor stimulation. We stimulated NIH3T3 OptoSOS cells with either constant activating red light or PDGF and measured transcriptional responses by RNAseq. Total mRNA was collected after 0, 30, 60 and 120 minutes and used to track the dynamics of transcript abundance in both conditions. Genes were defined as upregulated if they satisfied two criteria: (i) induced at least three-fold over unstimulated cells, and (ii) induced at least two consecutive timepoints. By these criteria we detected 118 genes that were upregulated within 2 h by either PDGF or light stimulation, a comparable number of Ras-responsive genes to that found in previous studies. We found that both PDGF and light induced nearly identical profiles of gene expression, with 100/118 genes induced by PDGF and 110/118 induced by light. At each time point we found excellent agreement between the levels of gene induction in response to both stimuli. This agreement also extended to response dynamics. where hierarchical clustering revealed three classes of dynamic response: an early response peaking within 30 min, an intermediate response peaking at ~1 h, and a late response where gene expression gradually increased over the full 2 h timecourse. In all three classes, we found that light and PDGF led to highly similar expression changes over time. We thus concluded that sole stimulation of the Ras/Erk pathway by light was sufficient to recapitulate at least the first two hours of the PDGF-induced transcriptional response. Overall design: RNA-seq to measure global transcript abundance at various timepoints after PDGF stimulation or direct optogenetic activation of Ras using the OptoSOS system in NIH3T3 cells (Toettcher et al, Cell 2013). 9 samples were collected using the TruSeq library preparation kit (Illumina), multiplexed, pooled and measured in 3 lanes of an Illumina Hi-Seq 2000. Library quality was assessed by Agilent Bioanalyzer. Roughly 30-50 million reads were measured per sample across all 3 lanes. Baseline transcript abundance was measured in triplicate (0 min controls) and each successive timepoint was measured in a single collection. Genes were considered upregulated if they were induced at least 5-fold in at least two consecutive timepoints relative to their baseline abundance.
Publication Title
Tracing Information Flow from Erk to Target Gene Induction Reveals Mechanisms of Dynamic and Combinatorial Control.
Sample Metadata Fields
Specimen part, Subject
View Samples- Mus musculus
- 12 Downloadable Samples
- Illumina HiSeq 2000
Description
In this experiment, we sought to analyze how the transcriptome of WT, ?5|6, and ?5|6:7|9 cells vary during differentiation of ESCs into cervical motor neurons Overall design: 3 lines (WT, ?5|6, ?5|6:7|9)
Publication Title
CTCF establishes discrete functional chromatin domains at the Hox clusters during differentiation.
Sample Metadata Fields
No sample metadata fields
View Samples