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SRP157750
Homo sapiens
39 Downloadable Samples
NextSeq 500
Description
The Alternative Lengthening of Telomeres (ALT) pathway stimulates telomere elongation and prevents cellular senescence in approximately 60% of osteosarcoma. While the precise mechanisms underlying the ALT pathway are unclear, mutations in the chromatin remodeling protein ATRX, histone chaperone DAXX, and the histone variant H3.3, correlate with ALT status. ATRX and DAXX facilitate deposition of the histone variant H3.3 within heterochromatic regions including the telomere suggesting that loss of ATRX, DAXX, and/or H3.3 lead to defects in heterochromatin maintenance at telomeres, ultimately contributing to ALT activity. Previous studies have detected genetic mutations in ATRX, DAXX, and H3.3 in ALT cell lines and tumor samples. However, a subset of ALT samples show loss of ATRX or DAXX protein expression or localization without evidence of genetic alterations, indicating a role for other defects in ATRX/DAXX/H3.3 function. Here, using Next Generation Sequencing, we identified a novel gene fusion event between DAXX and the kinesin motor protein, KIFC3, which leads to the translation of a chimeric DAXX-KIFC3 fusion protein. Here, we demonstrate that the fusion of KIFC3 to DAXX leads to defects in DAXX function and likely perpetuates ALT activity. These data highlight a previously unrecognized mechanism of DAXX inactivation in ALT positive osteosarcoma and provide rationale for thorough and comprehensive analyses of ATRX/DAXX/H3.3 proteins in ALT positive cancers. Overall design: 13 cell lines sequenced in triplicate, totaling 39 sequencing samples
Publication Title
Identification of a novel gene fusion in ALT positive osteosarcoma.
Sample Metadata Fields
Cell line, Subject
View Samples GSE24071- Mus musculus
- 8 Downloadable Samples
Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Overexpression of high mobility group AT-hook 2 (HMGA2) associated with truncations of its 3 untranslated region (UTR) with let-7 micro RNA-complementary sequences have been identified in patients with paroxysmal nocturnal hemoglobinuria (PNH). Here, we generated transgenic mice (Hmga2 mice) with a 3UTR-trncated Hmga2 cDNA that overexpress Hmga2 mRNA and protein in hematopoietic organs. Hmga2 mice showed proliferative hematopoiesis that mimicked a myeloproliferative neoplasm (MPN)-like phenotype with increased numbers of all lineages of peripheral blood cells, hypercellular bone marrow (BM), splenomegaly with extramedullary erythropoiesis, and erythropoietin-independent erythroid colony formation compared to wild-type mice. Hmga2 BM-derived cells took over most of hematopoiesis in competitive repopulations during serial BM transplants. When we bred mice with circulating PNH cells (Piga- mice) with Hmga2 mice, the lack of GPI-linked proteins did not add an additional clonal advantage to the Hmga2+ cells. In summary, our results showed that the overexpression of a 3UTR-truncated Hmga2 leads to a proliferative hematopoiesis with clonal advantage, which may explain clonal expansion in PNH or MPN at the level of HSC.
Publication Title
3'UTR-truncated Hmga2 cDNA causes MPN-like hematopoiesis by conferring a clonal growth advantage at the level of HSC in mice.
Sample Metadata Fields
Specimen part
View Samples- Danio rerio
- 6 Downloadable Samples
- IlluminaGenomeAnalyzerII, IlluminaHiSeq2000
Description
The Gata4 transcription factor is essential for normal heart development, but the molecular basis for its function remain poorly understood. We profiled at the whole genome level transcript changes in cardiomyocytes when Gata4 is depleted from zebrafish embryos. Our objective was to elucidate the cardiomyocyte-specific molecular program functioning downstream of Gata4 in order to better understand the role of Gata4 in cardiac morphogenesis. Overall design: Six samples in total are deposited. Three replicate control samples and three replicate Gata4 morphant samples were analyzed.
Publication Title
Small heat shock proteins Hspb7 and Hspb12 regulate early steps of cardiac morphogenesis.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
The retinal projection neurons, retinal ganglion cells (RGCs), can be categorized into distinct morphological and functional subtypes and by the laterality of their projections. Here, we used a new method for purifying the sparse population of ipsilaterally projecting RGCs in mouse retina from their contralaterally-projecting counterparts during embryonic development through rapid retrograde labeling followed by fluorescence-activated cell sorting (FACS). Through microarray analysis, we have uncovered the distinct molecular signatures that define and distinguish ipsilateral and contralateral RGCs during the critical period of axonal outgrowth and decussation, with over three hundred genes differentially experienced within these two cell populations. Amongst the genes upregulated in ipsilateral RGCs are many that are known to be expresed in progenitors cells and mark immaturity," including Math5 (Atoh7), Sox2, and cyclin D2. Many of these differentially regulated genes were subsequently validated via in vivo expression analysis. Thus, the molecular signatures of ipsilateral and contralateral RGCs and the mechanisms that regulate their differentiation are more diverse than previously expected.
Publication Title
Ipsilateral and Contralateral Retinal Ganglion Cells Express Distinct Genes during Decussation at the Optic Chiasm.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
mRNA expression differences between the liver and kidney of an adult male (homo sapien) were investigated using three technical replicates.
Publication Title
RNA-seq: an assessment of technical reproducibility and comparison with gene expression arrays.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 43 Downloadable Samples
- IlluminaHiSeq2000
Description
We had previously discovered that the transcription factor OVO-like 1 (OVOL1) was highly induced during trophoblast differentiation. In this study, we used an lentiviral shRNA strategy to decrease OVOL1 expression in BeWo trophoblast cells. Control cells were transduced with shRNAs targeting no known mammalian transcript (shCont). Following stimulation of differentiation (48h exposure to 8-bromo-cyclic adenosine monophosphate), a RNA-seq approach was used to determine global transcript differences in OVOL1-knockdown cells compared to control cells. Overall design: Trophoblast cells transduced with control shRNAs were used as controls. Cells transduced with shRNAs targeting OVOL1 were used as treatment. All cells received 250 uM 8-bromo-cyclic adenosine monophosphate to stimulate differentiation. Three independent replicates of control and treatment groups were analyzed.
Publication Title
OVO-like 1 regulates progenitor cell fate in human trophoblast development.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 23 Downloadable Samples
- Affymetrix Mouse Gene 2.0 ST Array (mogene20st)
Description
In two disparate models, we show that rapid revaccination following sublethal gamma radiation exposure rescues memory CD8+ T cell Responses.
Publication Title
Rescue of CD8+ T cell vaccine memory following sublethal γ irradiation.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 12 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Distinct processes govern the transition from myometrial quiescence to activation during both term and preterm labor. We sought the specific gene sets responsible for initiating term and preterm labor, along with a core set of effector genes necessary for labor independent of gestational age and the underlying trigger. The Effector Gene Set consisted of 49 genes present in both preterm and term labor but absent from non-labor samples. 122 genes were specific to preterm labor (Preterm Initiator Set) and 229 to term labor (Term Initiator Set). The Term Initiator and the Effector Sets reflected predominantly inflammatory processes. Surprisingly, the Preterm Initiator Gene Set reflected molecular and biological events almost exclusive of inflammation. Preterm and term labor differ dramatically in their unique, initiator gene profiles, suggesting alternative pathways underlie these events. Inflammatory processes are ubiquitous to the Term Initiator and the Effector Gene Sets, supporting the idea term parturition is an inflammatory process. The absence of inflammatory processes in the Preterm Initiator Set suggests inflammation is secondary to processes triggering spontaneous preterm birth, and could explain the lack of therapeutic efficacy associated with anti inflammatory/antibiotic regimens.
Publication Title
Human effector/initiator gene sets that regulate myometrial contractility during term and preterm labor.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
BeWo trophoblast cells differentiate in response to expsure to cyclic adenosine monophosphate (cAMP) analogs. Differentiation includes syncytialization (fusion) and hormonogenesis. The goal of this study was to globally determine transcripts differentially expressed in BeWo trophoblast cells following a 24-h exposure to 250 uM 8-bromo-cAMP.
Publication Title
OVO-like 1 regulates progenitor cell fate in human trophoblast development.
Sample Metadata Fields
Treatment
View Samples- Mus musculus
- 24 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Induced pluripotent stem (iPS) cells can be obtained from fibroblasts by expression of Oct4, Sox2, Klf4, and c-Myc. To determine how these factors induce this change in cell identity, we carried out genomewide promoter analysis of their binding in iPS and partially reprogrammed cells. Most targets in iPS cells are shared with ES cells and the factors cooperate to activate the ES-like expression program. In partially reprogrammed cells, genes bound by c-Myc have achieved a more ES-like binding and expression pattern. In contrast, genes that are co-bound by Oct4, Sox2, and Klf4 in ES cells and that encode pluripotency regulators show severe lack of both binding and transcriptional activation. Among the factors, c-Myc has a pivotal effect on the initiation of the ES transcription program, including the repression of fibroblast-specific genes. Our analysis begins to unravel how the four factors function together and suggests a temporal and separable order of their effects during reprogramming.
Publication Title
Role of the murine reprogramming factors in the induction of pluripotency.
Sample Metadata Fields
No sample metadata fields
View Samples