Synovial sarcoma-like tumors were generated in mice by conditionally expressing the human t(X;18) translocation-derived SYT-SSX2 fusion protein. Using a Tamoxifen-inducible CreER system, we show here that sporadic expression of SYT-SSX2 across multiple tissue types leads to exclusive formation of synovial sarcoma-like tumors while its widespread expression is lethal. CreER-based sporadic expression both avoids the severe early developmental phenotypes associated with widespread SYT-SSX2 expression and better models natural pathogenesis of cancers where transformed cells usually arise within an environment of largely normal cells.
A CreER-based random induction strategy for modeling translocation-associated sarcomas in mice.
No sample metadata fields
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Chromatin structure and gene expression programs of human embryonic and induced pluripotent stem cells.
Cell line
View SamplesKnowledge of both the global chromatin structure and the gene expression programs of human embryonic stem (ES) cells and induced pluripotent stem (iPS) cells should provide a robust means to assess whether the genomes of these cells have similar pluripotent states. Recent studies have suggested that ES and iPS cells represent different pluripotent states with substantially different gene expression profiles. We describe here a comparison of global chromatin structure and gene expression data for a panel of human ES and iPS cells. Genome-wide maps of nucleosomes with histone H3K4me3 and H3K27me3 modifications indicate that there is little difference between ES and iPS cells with respect to these marks. Gene expression profiles confirm that the transcriptional programs of ES and iPS cells show very few consistent differences. Although some variation in chromatin structure and gene expression was observed in these cell lines, these variations did not serve to distinguish ES from iPS cells.
Chromatin structure and gene expression programs of human embryonic and induced pluripotent stem cells.
Cell line
View SamplesTranscriptome profiling was performed on muscle biopsies from patients immediately before Total Knee Arthroplasty and two hours after TKA and tourniquet application. Overall design: RNA was isolated from 10 patients who were give vastus lateralis muscle biopsies immediately before surgery and 2 hours post surgery with tourniquet
Transcriptional profiling and muscle cross-section analysis reveal signs of ischemia reperfusion injury following total knee arthroplasty with tourniquet.
No sample metadata fields
View SamplesHoxb8 mutant mice show compulsive behavior similar to trichotillomania, a human obsessive-compulsive-spectrum disorder. The only Hoxb8 lineage-labeled cells in the brains of mice are microglia, suggesting that defective Hoxb8 microglia caused the disorder. What is the source of the Hoxb8 microglia? It has been posited that all microglia progenitors arise at embryonic day (E) 7.5 during yolk sac hematopoiesis, and colonize the brain at E9.5. In contrast, we show the presence of two microglia subpopulations: canonical, non-Hoxb8 microglia and Hoxb8 microglia. Unlike non- Hoxb8 microglia, Hoxb8 microglia progenitors appear to be generated during the second wave of yolk sac hematopoiesis, then detected in the aorto-gonad-mesonephros (AGM) and fetal liver, where they are greatly expanded, prior to infiltrating the E12.5 brain. Further, we demonstrate that Hoxb8 hematopoietic progenitor cells taken from fetal liver are competent to give rise to microglia in vivo. Although the two microglial subpopulations are very similar molecularly, and in their response to brain injury and participation in synaptic pruning, they show distinct brain distributions which might contribute to pathological specificity. Non-Hoxb8 microglia significantly outnumber Hoxb8 microglia, but they cannot compensate for the loss of Hoxb8 function in Hoxb8 microglia, suggesting further crucial differences between the two subpopulations. Overall design: Green (non-Hoxb8, control) and yellow (Hoxb8, experimental) microglia data sets
Correction: Two distinct ontogenies confer heterogeneity to mouse brain microglia (doi: 10.1242/dev.152306).
Age, Specimen part, Cell line, Subject
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Cross-species gene expression analysis identifies a novel set of genes implicated in human insulin sensitivity.
Specimen part, Time
View SamplesRecent discovery reveals HFD insult can cause insulin resistance very rapidly, but the underlying mechanism is still not well understood. We performed a short term experiment in a Diet Induced Insulin resistance mouse model.
Cross-species gene expression analysis identifies a novel set of genes implicated in human insulin sensitivity.
Specimen part, Time
View SamplesTo dissect the impact of nuclear and extranuclear mutant htt on the initiation and progression of disease, we generated a series of transgenic mouse lines in which nuclear localization (NLS) or nuclear export sequences (NES) have been placed N-terminal to the htt exon 1 protein carrying 144 glutamines. Our data indicate that the exon 1 mutant protein is present in the nucleus as part of an oligomeric or aggregation complex. Increasing the concentration of the mutant transprotein in the nucleus is sufficient for, and dramatically accelerates the onset and progression of behavioral phenotypes. Furthermore, nuclear exon 1 mutant protein is sufficient to induce cytoplasmic neurodegeneration and transcriptional dysregulation. However, our data suggests that cytoplasmic mutant exon 1 htt, if present, contributes to disease progression.
Contribution of nuclear and extranuclear polyQ to neurological phenotypes in mouse models of Huntington's disease.
No sample metadata fields
View SamplesInduced pluripotent stem cells (iPSCs) derived from somatic cells of patients by viral vector-mediated factor transduction represent a powerful tool for biomedical research and may provide a source for cell replacement therapies. However, the proviruses encoding the reprogramming factors represent a major limitation of the current technology because even low vector expression may alter the differentiation potential of the iPSCs and induce malignant transformation. Here we show that fibroblasts from five patients with idiopathic Parkinsons disease (PD) can be efficiently reprogrammed into hiPSCs and subsequently differentiated into dopaminergic neurons. Moreover, we derived PD specific hiPSCs free of reprogramming factors using Cre-recombinase excisable viruses. Upon factor deletion these cells maintain a pluripotent state and intact karyotype. Importantly, these factor-free hiPSCs show a global gene expression profile, which is more closely related to hESCs than to hiPSCs carrying the transgenes. Our results indicate that residual transgene expression in conventional virus-carrying hiPSCs can affect their molecular characteristics and that factor-free hiPSCs therefore represent a more suitable source of cells for modeling of human disease.
Parkinson's disease patient-derived induced pluripotent stem cells free of viral reprogramming factors.
No sample metadata fields
View SamplesExpression profiles of acute myeloid leukemia patient samples.
Identification of genes with abnormal expression changes in acute myeloid leukemia.
No sample metadata fields
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