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GSE17964
Macaca mulatta
12 Downloadable Samples
Affymetrix Rhesus Macaque Genome Array (rhesus)
Description
Parthenogenetic embryonic stem cells (PESCs) may have future utility in cell replacement therapies. We examined genome-wide mRNA expression profiles of monkey PESCs relative to ESCs derived from fertilized embryos. Several known paternally-imprinted genes were in the highly down-regulated group in PESCs compared to ESCs. Allele specific expression analysis of paternally-imprinted genes, i.e., those genes whose expression is down-regulated in PESCs, led to the identification of one novel candidate that was exclusively expressed from a paternal allele. Our findings suggest that PESCs could be used as a model for studying genomic imprinting and in the discovery of novel imprinted genes.
Publication Title
Discovery of a novel imprinted gene by transcriptional analysis of parthenogenetic embryonic stem cells.
Sample Metadata Fields
Sex, Specimen part
View Samples- Macaca mulatta
- 14 Downloadable Samples
- Affymetrix Rhesus Macaque Genome Array (rhesus)
Description
Derivation of embryonic stem cells (ESC) genetically identical to a patient by somatic cell nuclear transfer (SCNT) holds the potential to cure or alleviate the symptoms of many degenerative diseases while circumventing any immunorejection issues. However, no primate nuclear transfer embryonic stem (ntES) cell lines have been derived to date. Here, we used a modified SCNT technique to produce rhesus macaque SCNT blastocysts at a relatively high efficiency from adult donor cells and we successfully derived two primate ntES cell lines from 304 oocytes (an overall efficiency of 0.7%). Nuclear and mitochondrial DNA analysis confirmed the ntES cell lines were derived from rhesus monkey SCNT blastocysts and both rhesus monkey ntES cell lines exhibited a normal ESC morphology, expressed key stemness markers, were transcriptionally indistinguishable from control ESC lines and differentiated into multiple cell types. This is, to our knowledge, the first confirmed derivation of primate ntES cell lines.
Publication Title
Producing primate embryonic stem cells by somatic cell nuclear transfer.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 19 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Medulloblastoma is a malignant brain tumor that occurs predominantly in children. Current risk stratification based on the clinical parameters is inadequate for accurate prognostication. In order to get a better understanding of medulloblastoma biology, miRNA profiling of medulloblastomas was carried out in parallel with the expression profiling of protein- coding genes.
Publication Title
Distinctive microRNA signature of medulloblastomas associated with the WNT signaling pathway.
Sample Metadata Fields
Sex
View Samples- Mus musculus
- 10 Downloadable Samples
Illumina HiSeq 2500
Description
Regulatory T cells (Tregs) play a cardinal role in the immune system by suppressing detrimental autoimmune responses, but their role in acute and chronic infectious diseases remains unclear. We recently demonstrated that IFN-??? receptor (IFNAR) signaling promotes Treg function in autoimmunity. To dissect the functional role of IFNAR-signaling in Tregs during acute and chronic viral infection, we infected Treg-specific IFNAR deficient (IFNARfl/flxFoxp3YFP-Cre) mice with LCMV Armstrong and Clone-13. In both models, IFNARfl/flxFoxp3YFP-Cre mice Tregs expressed enhanced expression of Treg associated activation antigens. The enhanced activated phenotype was also seen when we compared the transcriptomes of IFNARfl/flxFoxp3YFP-Cre and wild type (WT) Tregs by RNA-Seq on day 25-post Clone-13 infection. LCMV-specific CD8+ T cells from IFNARfl/flxFoxp3YFP-Cre mice produced less antiviral IFN? and TNF? in both acute and chronic LCMV. In the chronic model, the numbers of anti-viral effector and memory CD8+ T cells were decreased in IFNARfl/flxFoxp3YFP-Cre mice and the effector CD4+ and CD8+ T cells exhibited a phenotype compatible with enhanced exhaustion. IFNARfl/flxFoxp3YFP-Cre mice cleared Armstrong infection normally, but had higher viral titers in sera, kidneys and lungs than WT mice during chronic infection. Thus, type I IFN signaling in Tregs is context-dependent, resulting in enhanced suppressor function in some models of autoimmunity, but decreased suppressor function in acute and chronic viral infection. Overall design: mRNA from Treg cells from 5 WT and 5 IFNAR deficient mice were analyzied by RNA-seq using Illumina HiSeq
Publication Title
Type I interferon signaling attenuates regulatory T cell function in viral infection and in the tumor microenvironment.
Sample Metadata Fields
Cell line, Subject
View Samples- Homo sapiens
- 4 Downloadable Samples
- Illumina HiSeq 2500
Description
Human embryonic stem cells (hESC) display substantial heterogeneity in gene expression, implying the existence of discrete substates within the stem cell compartment. To determine whether these substates impact fate decisions of hESC we used a GFP reporter line to investigate the properties of fractions of putative undifferentiated cells defined by their differential expression of the endoderm transcription factor, GATA6, together with the hESC surface marker, SSEA3. By single cell cloning, we confirmed that substates characterized by expression of GATA6 and SSEA3 include pluripotent stem cells capable of long term self-renewal. When clonal stem cell colonies were formed from GATA6-positive and GATA6-negative cells, more of those derived from GATA6-positive cells contained spontaneously differentiated endoderm cells than similar colonies derived from the GATA6-negative cells. We characterized these discrete cellular states using single cell transcriptomic analysis, identifying a potential role for SOX17 in the establishment of the endoderm biased stem cell state. Overall design: Examination of 4 different cell substates within one human embryonic stem cell line as determine by the expression status of GATA6 and SSEA3
Publication Title
Identification and Single-Cell Functional Characterization of an Endodermally Biased Pluripotent Substate in Human Embryonic Stem Cells.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 6 Downloadable Samples
- NextSeq 500
Description
Malignant rhabdoid tumors (MRT) are highly aggressive pediatric cancers that respond poorly to current therapies. We screened several MRT cell lines each with large-scale RNAi, CRISPR-Cas9, and small-molecule libraries to identify potential drug targets specific for these cancers. We discovered MDM2 and MDM4, the canonical negative regulators of p53, as significant vulnerabilities. Using two compounds currently in clinical development, idasanutlin and ATSP-7041, we show that MRT cells are more sensitive than other p53 wild-type cancer cell lines to MDM2 and dual MDM2/4 inhibition in vitro. These compounds cause significant upregulation of the p53 pathway in MRT cells, and sensitivity is ablated by CRISPR-Cas9-mediated inactivation of TP53. We show that loss of SMARCB1, a subunit of the SWI/SNF (BAF) complex mutated in nearly all MRT, sensitizes cells to MDM2 and MDM2/4 inhibition by enhancing p53-mediated apoptosis. Both MDM2 and MDM2/4 inhibition slowed MRT xenograft growth in vivo, with a five-day idasanutlin pulse causing marked regression of all xenografts including durable complete responses in 50% of mice. Together, these studies identify a genetic connection between mutations in the SWI/SNF chromatin-remodeling complex and the tumor suppressor gene p53, and provide preclinical evidence to support the targeting of MDM2 and MDM4 in this often-fatal pediatric cancer. Overall design: RNA-seq in TTC642 MRT cells treated with idasanutlin compared to DMSO
Publication Title
MDM2 and MDM4 Are Therapeutic Vulnerabilities in Malignant Rhabdoid Tumors.
Sample Metadata Fields
Specimen part, Subject
View Samples- Mus musculus
- 4 Downloadable Samples
- Illumina Genome Analyzer IIx
Description
We applied a 5''RNA-seq methodology to assess gene and differential isoform expression in striated muscle tissues extracted from adult wild-type mice. Overall design: 5''RNA-seq analysis of transcriptomes from mouse soleus, tibialis anterior (TA), diaphragm and left ventricle myocardial tissues. Three biological replicates per tissue were pooled into a single sequencing run. 5''RNA-seq methodology consists of enhanced sequencing of 5'' ends and computational assessment of changes at start-sites of genes.
Publication Title
Tropomodulin 1 directly controls thin filament length in both wild-type and tropomodulin 4-deficient skeletal muscle.
Sample Metadata Fields
Sex, Specimen part, Cell line, Subject
View Samples- Mus musculus
- 10 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
The goal of this study is to uncover the changes in the transcriptome of sensory neurons of the liver kinase B1 (LKB1) knockout
Publication Title
Regulation of axonal morphogenesis by the mitochondrial protein Efhd1.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
- Illumina MouseWG-6 v2.0 expression beadchip
Description
Genome-wide gene expression analysis on tibialis anterior muscle from 2-month-old nebulin SH3 domain deleted (NebSH3) mice compared to wildtype.
Publication Title
The nebulin SH3 domain is dispensable for normal skeletal muscle structure but is required for effective active load bearing in mouse.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Homo sapiens
- 6 Downloadable Samples
- Illumina HiSeq 2500
Description
Cellular replicative senescence, a state of permanent cell-cycle arrest that occurs following an extended period of cell division in culture, has been linked to organismal aging, tissue repair and tumorigenesis. In this study, we comparatively investigated the global lipid profiles and mRNA content of proliferating and senescent-state BJ fibroblast cells. We found that both the expression levels of lipid-regulating genes, as well as the abundance of specific lipid families, are actively regulated. We further found that 19 polyunsaturated triacylglycerol species showed the most prominent changes during replicative senescence. We argue that diversion of polyunsaturated fatty acids to glycerolipid biosynthesis could be responsible for the accumulation of specific triacylglycerols. This, in turn, could be one of the cellular mechanisms to prevent lipotoxicity under increased oxidative stress conditions observed during replicative senescence. Collectively, our results place regulation of specific lipid species to a central role during replicative senescence. Overall design: We sequence total RNA from 3 early PD and 3 senesent human BJ cell lines to detect the expressional differences between early PD and senescent cells.
Publication Title
Regulation of lipids is central to replicative senescence.
Sample Metadata Fields
Specimen part, Subject
View Samples