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GSE26212
Homo sapiens
82 Downloadable Samples
Illumina HumanHT-12 V3.0 expression beadchip
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
The effects of EBV transformation on gene expression levels and methylation profiles.
Sample Metadata Fields
Sex, Specimen part, Subject
View Samples- Homo sapiens
- 82 Downloadable Samples
- Illumina HumanHT-12 V3.0 expression beadchip
Description
Epstein-Barr virus (EBV)-transformed lymphoblastoid cell lines (LCLs) provide a conveniently accessible and renewable resource for functional studies in humans. The ability to accumulate multidimensional data pertaining to the same individual cell lines, from complete genomic sequences to detailed gene regulatory profiles, further enhances the utility of LCLs as a model system. A lingering concern, however, is that the changes associated with EBV transformation of LCLs reduce the usefulness of LCLs as a surrogate model for primary tissues. To evaluate the validity of this concern, we compared global gene expression profiles between CD20+ primary B cells and CD3+ primary T cells sampled from six individuals. Six independent replicates of transformed LCLs were derived from each sample.
Publication Title
The effects of EBV transformation on gene expression levels and methylation profiles.
Sample Metadata Fields
Sex, Specimen part, Subject
View Samples- Homo sapiens
- 26 Downloadable Samples
Illumina HiSeq 2000
Description
Reprogramming human somatic cells into induced pluripotent stem cells (iPSC) has been suspected of causing de novo copy number variations (CNVs). To explore this issue, we performed a whole-genome and transcriptome analysis of 20 human iPSC lines derived from primary skin fibroblasts of 7 individuals using next-generation sequencing. We find that, on average, an iPSC line manifests two CNVs not apparent in the fibroblasts from which the iPSC was derived. Using qPCR, PCR, and digital droplet PCR (ddPCR) to amplify across the CNVs'' breakpoints, we show that at least 50% of those CNVs are present as low frequency somatic genomic variants in parental fibroblasts and are manifested in iPSC colonies due to their clonal origin. Hence, reprogramming does not necessarily lead to de novo CNVs in iPSC, since most of line-manifested CNVs reflect somatic mosaicism in the human skin. Moreover, our findings demonstrate that clonal expansion, and iPSC lines in particular, can be used as a discovery tool to reliably detect low frequency CNVs in the tissue of origin. Overall, we estimate that approximately 30% of the fibroblast cells have somatic CNVs, suggesting widespread somatic mosaicism in the human body. Our study paves the way to understanding the fundamental question of the extent to which cells of the human body normally acquire structural alterations in their DNA post-zygotically. Overall design: We have generated and characterized hiPSC lines derived from skin fibroblasts collected from seven members of two families, which were competent to be differentiated into neuronal progenitors and neurons
Publication Title
Somatic copy number mosaicism in human skin revealed by induced pluripotent stem cells.
Sample Metadata Fields
Specimen part, Subject
View Samples- Danio rerio
- 15 Downloadable Samples
- Affymetrix Zebrafish Genome Array (zebrafish)
Description
Investigating neuronal and photoreceptor regeneration in the retina of zebrafish has begun to yield insights into both the cellular and molecular means by which this lower vertebrate is able to repair its central nervous system. However, knowledge about the signaling molecules in the local microenvironment of a retinal injury and the transcriptional events they activate during neuronal death and regeneration is still lacking. To identify genes involved in photoreceptor regeneration, we combined light-induced photoreceptor lesions, laser-capture microdissection (LCM) of the outer nuclear layer (ONL) and analysis of gene expression to characterize transcriptional changes for cells in the ONL as photoreceptors die and are regenerated. Using this approach, we were able to characterize aspects of the molecular signature of injured and dying photoreceptors, cone photoreceptor progenitors and microglia within the ONL. We validated changes in gene expression and characterized the cellular expression for three novel, extracellular signaling molecules that we hypothesize are involved in regulating regenerative events in the retina.
Publication Title
Identification of the molecular signatures integral to regenerating photoreceptors in the retina of the zebra fish.
Sample Metadata Fields
No sample metadata fields
View Samples- Arabidopsis thaliana
- 18 Downloadable Samples
- Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)
Description
Plants regulate their time to flowering by gathering information from the environment. Photoperiod and temperature are among the most important environmental variables. Suboptimal, but not near-freezing, temperatures regulate flowering through the thermosensory pathway, which overlaps with the autonomous pathway. Here we show that ambient temperature regulates flowering by two genetically distinguishable pathways, one that requires TFL1 and another that requires ELF3. The delay in flowering time observed at lower temperatures was partially suppressed in single elf3 and tfl1 mutants, whereas double elf3 tfl1 mutants were insensitive to temperature. tfl1 mutations abolished the temperature response in cryptochrome mutants that are deficient in photoperiod perception, but not in phyB mutants that have a constitutive photoperiodic response. Contrary to tfl1, elf3 mutations were able to suppress the temperature response in phyB mutants, but not in cryptochrome mutants. The gene expression profile revealed that the tfl1 and elf3 effects are due to the activation of different sets of genes and identified CCA1 and SOC1/AGL20 as being important cross talk points. Finally, genome-wide gene expression analysis strongly suggests a general and complementary role for ELF3 and TFL1 in temperature signalling.
Publication Title
A complementary role for ELF3 and TFL1 in the regulation of flowering time by ambient temperature.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 18 Downloadable Samples
- Affymetrix Human Genome U95 Version 2 Array (hgu95av2)
Description
Human Burkitt's lymphoma ST486 cells were transduced with non-target control shRNA lentiviral vectors, FOXM1 shRNA, and MYB shRNA lentiviral vectors. Total RNA was isolated 24h later. cRNA was produced with the standard one-step IVT protocol (Affymetix) and hybridized in U95Av2 gene chips (Affymetrix).
Publication Title
Correlating measurements across samples improves accuracy of large-scale expression profile experiments.
Sample Metadata Fields
Cell line, Time
View Samples- Danio rerio
- 8 Downloadable Samples
- Affymetrix Zebrafish Genome Array (zebrafish)
Description
In the retina of adult teleosts, stem cells are sustained in two specialized niches: the ciliary marginal zone (CMZ) and the microenvironment surrounding adult Mller glia. Recently, Mller glia were identified as the regenerative stem cells in the teleost retina. Secreted signaling molecules that regulate neuronal regeneration in the retina are largely unknown. In a microarray screen to discover such factors, we identified midkine-b (mdkb). Midkine is a highly conserved heparin-binding growth factor with numerous biological functions. The zebrafish genome encodes two distinct midkine genes: mdka and mdkb. Here, we describe the cellular expression of mdka and mdkb during retinal development and the initial, proliferative phase of photoreceptor regeneration. The results show that in the embryonic and larval retina mdka and mdkb are expressed in stem cells, retinal progenitors and neurons in distinct patterns that suggest different functions for the two molecules. Following the selective death of photoreceptors in the adult, mdka and mdkb are co-expressed in horizontal cells and proliferating Mller glia and their neurogenic progeny. These data reveal that Mdka and Mdkb are signaling factors present in the retinal stem cell niches in both embryonic and mature retinas, and that their cellular expression is actively modulated during retinal development and regeneration.
Publication Title
Cellular expression of midkine-a and midkine-b during retinal development and photoreceptor regeneration in zebrafish.
Sample Metadata Fields
No sample metadata fields
View Samples- Arabidopsis thaliana
- 12 Downloadable Samples
- Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)
Description
Two aspects of light are very important for plant development: the length of the light phase or photoperiod and the quality of incoming light. Photoperiod detection allows plants to anticipate the arrival of the next season, whereas light quality, mainly the red to far-red ratio (R:FR), is an early signal of competition by neighbouring plants. phyB represses flowering by antagonising CO at the transcriptional and post-translational levels. A low R:FR decreases active phyB and consequently increases active CO, which in turn activates the expression of FT, the plant florigen. Other phytochromes like phyD and phyE seem to have redundant roles with phyB. PFT1, the MED25 subunit of the plant Mediator complex, has been proposed to act in the light-quality pathway that regulates flowering time downstream of phyB. However, whether PFT1 signals through CO and its specific mechanism are unclear. Here we show that CO-dependent and -independent mechanisms operate downstream of phyB, phyD and phyE to promote flowering, and that PFT1 is equally able to promote flowering by modulating both CO-dependent and -independent pathways. Our data are consistent with the role of PFT1 as an activator of CO transcription, and also of FT transcription, in a CO-independent manner. Our transcriptome analysis is also consistent with CO and FT genes being the most important flowering targets of PFT1. Furthermore, comparison of the pft1 transcriptome with transcriptomes after fungal and herbivore attack strongly suggests that PFT1 acts as a hub, integrating a variety of interdependent environmental stimuli, including light quality and jasmonic acid-dependent defences.
Publication Title
PFT1, the MED25 subunit of the plant Mediator complex, promotes flowering through CONSTANS dependent and independent mechanisms in Arabidopsis.
Sample Metadata Fields
Specimen part
View Samples- Saccharomyces cerevisiae
- 4 Downloadable Samples
- Illumina HiSeq 2000
Description
Transcriptome study of 2 Saccharomyces cerevisiae W303 derivatives, one carrying GFP (control) and one carrying aSyn-GFP
Publication Title
Different 8-hydroxyquinolines protect models of TDP-43 protein, α-synuclein, and polyglutamine proteotoxicity through distinct mechanisms.
Sample Metadata Fields
Specimen part, Disease, Cell line
View Samples- Homo sapiens
- 24 Downloadable Samples
- Affymetrix Human Transcriptome Array 2.0 (hta20)
Description
Tumor protein p53 is a key regulator of several cellular pathways, including DNA repair, cell cycle and angiogenesis. Kevetrin exhibits p53-dependent as well as independent activity in solid tumors, while its effects on leukemic cells remain unknown. We analyzed the response of acute myeloid leukemia (AML) cell lines (TP53 wild-type: OCI-AML3 and MOLM-13; and TP53-mutant: KASUMI-1 and NOMO-1) to kevetrin at a concentration range of 85-340 μM. Kevetrin induced cell growth arrest and apoptosis in all cell lines and in primary cells, with TP53-mutant models displaying a higher sensitivity and p53 induction. Gene expression profiling revealed a common core transcriptional program altered by drug exposure and the downregulation of glycolysis, DNA repair and unfolded protein response signatures. These findings suggest that kevetrin may be a promising therapeutic option for patients with both wild-type and TP53-mutant AML.
Publication Title
Kevetrin induces apoptosis in TP53 wild‑type and mutant acute myeloid leukemia cells.
Sample Metadata Fields
Treatment
View Samples