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GSE62593
Homo sapiens
12 Downloadable Samples
Affymetrix Human Exon 1.0 ST Array [transcript (gene) version (huex10st)
Description
CCRF_CEM cell line was treated by AB61 which is potent cytotoxic compound, as the positive controls were used tubercidin and actinomycin D.
Publication Title
7-(2-Thienyl)-7-Deazaadenosine (AB61), a New Potent Nucleoside Cytostatic with a Complex Mode of Action.
Sample Metadata Fields
Cell line
View Samples- Mus musculus
- 7 Downloadable Samples
- Affymetrix Mouse Gene 2.0 ST Array (mogene20st)
Description
Cellular reprogramming from somatic cells to induced pluripotent stem cells (iPSCs) can be achieved through forced expression of the transcription factors Oct4, Klf4, Sox2 and c-Myc (OKSM). These factors, in combination with environmental cues, induce a stable intrinsic pluripotency network that confers indefinite self-renewal capacity on iPSCs. In addition to Oct4 and Sox2, the homeodomain-containing transcription factor Nanog is an integral part of the pluripotency network. Although Nanog expression is not required for the maintenance of pluripotent stem cells, it has been reported to be essential for the establishment of both embryonic stem cells (ESCs) from blastocysts and iPSCs from somatic cells. Here we revisit the role of Nanog in direct reprogramming. Surprisingly, we find that Nanog is dispensable for iPSC formation under optimized culture conditions. We further document that Nanog-deficient iPSCs are transcriptionally highly similar to wild-type iPSCs and support the generation of teratomas and chimeric mice. Lastly, we provide evidence that the presence of ascorbic acid in the culture media is critical for overcoming the previously observed reprogramming block of Nanog knockout cells.
Publication Title
Nanog is dispensable for the generation of induced pluripotent stem cells.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 5 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
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.
Publication Title
A CreER-based random induction strategy for modeling translocation-associated sarcomas in mice.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 30 Downloadable Samples
- Affymetrix Murine Genome U74A Version 2 Array (mgu74av2)
Description
Three cell types, intermediolateral column motoneurons, medial motoneurons, and lateral motoneurons were isolated from a single adult spinal cord using laser capture microscopy. Four hundred captures were collected for each cell type. For a given cell type, RNA was extracted from the 400 captures using an Arcturus picopure kit. RNA was split in half and two targets were produced using a double amplification protocol. Each target was hybridized to Affymetrix chips and signals were normalized with R-pack. Inverse logs are provided. Five animals were used in these experiments, and all three cell types were collected from each animal. Thus, for each cell type, there are five biological replicates, and for each biological replicate there are two technical replicates. In all thirty chips were analyzed. Techinical replicates are indicated as Set 1 and Set 2. Animal numbers are indicated by Pair1 through Pair 5.
Publication Title
Divergence between motoneurons: gene expression profiling provides a molecular characterization of functionally discrete somatic and autonomic motoneurons.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 19 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Direct reprogramming of human fibroblasts to a pluripotent state has been achieved through ectopic expression of the transcription factors OCT4, SOX2, and either cMYC and KLF4 or NANOG and LIN28. Little is known, however, about the mechanisms by which reprogramming occurs, which is in part limited by the low efficiency of conversion. To this end, we sought to create a doxycycline-inducible lentiviral system to convert primary human fibroblasts and keratinocytes into human induced pluripotent stem (hiPS) cells. hiPS cells generated with this system were molecularly and functionally similar to human embryonic stem (hES) cells, demonstrated by gene expression profiles, DNA methylation status, and differentiation potential. While expression of the viral transgenes was required for several weeks in fibroblasts, we found that 10 days was sufficient for the reprogramming of keratinocytes, suggesting that the kinetics of reprogramming are cell-type dependent. Using our inducible system, we developed a strategy to induce hiPS cell formation at high frequency by generating differentiated cells that contain the viral transgenes in a pattern that enables successful induction of pluripotency. Upon addition of doxycycline to differentiated hiPS-derived cells, we obtained secondary hiPS cells at a frequency at least 100-fold greater than the initial conversion. The ability to reprogram cells with high efficiency provides a unique platform to dissect the underlying molecular and biochemical processes that accompany nuclear reprogramming.
Publication Title
A high-efficiency system for the generation and study of human induced pluripotent stem cells.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 18 Downloadable Samples
IlluminaHiSeq2000
Description
OBJECTIVE: Acromegaly is a rare endocrine disorder with excess growth hormone (GH) production. This disorder has important metabolic effects in insulin resistance and lipolysis. The objective of this study was to explore transcriptional changes induced by GH in adipose tissue. METHODS: The patients underwent clinical and metabolic profiling including assessment of HOMA-IR. Explants of adipose tissue were assayed ex-vivo for lipolysis and ceramide levels. Adipose tissue was analyzed by RNA sequencing (RNA-seq). RESULTS: There was evidence of reduced insulin sensitivity based on the increase in fasting glucose, insulin and HOMA-IR score. We observed several previously reported transcriptional changes (IGF1, IGFBP3) as well as several novel transcriptional changes, some of which may be important for GH signal regulation (PTPN3 and PTPN4) and the effect of GH on growth and proliferation. Several transcripts could potentially be important in GH-induced metabolic changes. Specifically, induction of LPL, ABHD5, and ACVR1C could contribute to enhanced lipolysis and may explain the suggestive enhancement of adipose tissue lipolysis in acromegaly patients as reflected by glycerol release from the explants of the two groups of patients (p=0.09). Higher expression of SCD and TCF7L2 could contribute to insulin resistance. Expression of HSD11B1 was reduced and GR was increased, predicting modified glucocorticoid activity in acromegaly. CONCLUSIONS: We identified the acromegaly gene expression signature in human adipose tissue. The significance of altered expression of specific transcripts will enhance our understanding of the metabolic and proliferative changes associated with acromegaly. Overall design: DESIGN: Patients with acromegaly (n=9) or non-functioning pituitary adenoma (n=11) were prospectively observed from March 2011 to June 2012. Sequencing was performed on RNA from 7 acromegaly patients and 11 controls.
Publication Title
Gene Expression Signature in Adipose Tissue of Acromegaly Patients.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Clariom S Array (clariomsmouse)
Description
To assess the role of the aryl hydrocarbon receptor (AHR) receptor in dendritic epidermal T cells (DETC), we sorted DETC from 2 weeks old mice homozygous and heterozygous for AHR-knockout. While DETC are not maintained in the epidermis of mice with a homozygous AHR-knockout, those in heterozygous mice devellop normally. The age at 2 weeks is critical for the DETC establishment and the peak time of the so-called proliferation burst of DETC in wildtype mice. DETC were identified in epidermal cell suspension by expression of the gamma-delta T cell receptor. The DETC proportion of live epidermal cells was between 10-15 % in Ahr-het and 2-4 % in Ahr-ko mice. After FACS-sorting to a purity of 90-98 %, DETC were lysed and their RNA was extracted. Three RNA samples for each genotype were generated, by pooling the RNA of 2-3 mice for each sample. RNA was processed and hybridized to Applied BiosystemsTM ClariomTM S Mouse Gene Expression Microarrays. Using the Software package R the data were normalized using the Robust Multichip Average algorithm (RMA) and significance of differentially regulated genes was assessed by the False Discovery Rate (FDR) using the Benjamini and Hochberg’s method.
Publication Title
The small chain fatty acid butyrate antagonizes the TCR-stimulation-induced metabolic shift in murine epidermal gamma delta T cells.
Sample Metadata Fields
Age, Specimen part
View Samples- Homo sapiens
- 42 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Chromatin structure and gene expression programs of human embryonic and induced pluripotent stem cells.
Sample Metadata Fields
Cell line
View Samples- Saccharomyces cerevisiae
- 49 Downloadable Samples
- Illumina HiSeq 2500
Description
In response to acute loss of the Ulp2 SUMO-specific protease, yeast become disomic for chromosome I (ChrI) and ChrXII. Here we report that ChrI disomy, which creates an adaptive advantage in part by increasing the dosage of the Ccr4 deadenylase, was eliminated by extended passaging. Loss of aneuploidy is often accompanied by mutations in essential SUMO-ligating enzymes, which reduced polySUMO-conjugate accumulation. The mRNA levels for almost all ribosomal proteins increases transiently upon initial loss of Ulp2, but elevated Ccr4 levels limit excess ribosome formation. Notably, extended passaging leads to increased levels of many small nucleolar RNAs (snoRNAs) involved in ribosome biogenesis, and higher dosage of three linked ChrXII snoRNA genes suppressed ChrXII disomy in ulp2? cells. Our data reveal that aneuploidy allows rapid adaptation to Ulp2 loss, but long-term adaptation restores euploidy. Cellular evolution restores homeostasis through countervailing mutations in SUMO-modification pathways and regulatory shifts in ribosome biogenesis. Overall design: In these comparisons, the ulp2? cells either carried a WT ULP2 plasmid or empty vector and were passaged for 50 or 500 generations. mRNA profiles of them were generated by sequencing, in triplicate, using Illumina HiSeq 2500 .
Publication Title
Distinct adaptive mechanisms drive recovery from aneuploidy caused by loss of the Ulp2 SUMO protease.
Sample Metadata Fields
Subject
View Samples- Homo sapiens
- 42 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Knowledge 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.
Publication Title
Chromatin structure and gene expression programs of human embryonic and induced pluripotent stem cells.
Sample Metadata Fields
Cell line
View Samples