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GSE48275
Homo sapiens
16 Downloadable Samples
Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Since the initial discovery that OCT4, SOX2, KLF4 and c-MYC overexpression sufficed for the induction of pluripotency in somatic cells, methodologies replacing the original factors have enhanced our understanding of the reprogramming process. However, unlike in mouse, OCT4 has not been replaced successfully during reprogramming of human cells. Here we report on a strategy to do so. Through a combination of transcriptome and bioinformatic analysis we have identified factors previously characterized as being lineage specifiers that are able to replace OCT4 and SOX2 in the reprogramming of human fibroblasts. Our results show that is possible to replace OCT4 and SOX2 simultaneously with alternative lineage specifiers in the reprogramming of human cells. At a broader level, they also support a model in which counteracting lineage specification networks underlie the induction of pluripotency,
Publication Title
Reprogramming of human fibroblasts to pluripotency with lineage specifiers.
Sample Metadata Fields
Specimen part
View Samples- Saccharomyces cerevisiae
- 17 Downloadable Samples
- Affymetrix Yeast Genome S98 Array (ygs98)
Description
Diurnal temperature cycling is an intrinsic characteristic of many exposed microbial ecosystems. However, its influence on yeast physiology and transcriptome has not been studied in detail. In this study, 24-h sinoidal temperature cycles, oscillating between 12 and 30C, were imposed on anaerobic, glucose-limited chemostat cultures of Saccharomyces cerevisiae. After three diurnal temperature cycles (DTC), concentrations of glucose, and extracellular metabolites, as well as CO2-production rates showed regular, reproducible circadian rhytms. DTC also led to waves of transcriptional activation and repression, which involved one sixth of the yeast genome. A substantial fraction of these DTC-responsive genes appeared to primarily respond to changes in glucose concentration. Elimination of known glucose-responsive genes revealed overrepresentation of previously identified temperature-responsive genes as well as genes involved in cell cycle and de novo purine biosynthesis. Analyses of budding index and flow cytomery demonstrated that DTC led to a partial synchronization of the cell cycle of the yeast populations in the chemostat cultures, which was lost upon release from DTC. Comparison of DTC results with data from steady-state cultures showed that DTC was sufficiently slow to allow S. cerevisiae chemostat cultures to almost completely acclimatize their transcriptome and physiology at the DTC temperature maximum, and to approach acclimation at the DTC temperature minimum.
Publication Title
Physiological and transcriptional responses of anaerobic chemostat cultures of Saccharomyces cerevisiae subjected to diurnal temperature cycles.
Sample Metadata Fields
No sample metadata fields
View Samples- Arabidopsis thaliana
- 6 Downloadable Samples
- Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)
Description
Systemic transcriptional responses in Arabidopsis thaliana distal leaves to wounding
Publication Title
The plant NADPH oxidase RBOHD mediates rapid systemic signaling in response to diverse stimuli.
Sample Metadata Fields
Age, Specimen part
View Samples- Homo sapiens
- 40 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Gain-of-function mutations in NOTCH1 are common in T-cell lymphoblastic leukemias making this receptor a promising target for drugs such as gamma-secretase inhibitors (GSI), which block a proteolytic cleavage required for NOTCH1 activation. However, the enthusiasm for these therapies has been tempered by tumor resistance and the paucity of information on the oncogenic programs regulated by oncogenic NOTCH1. Analysis of gene expression in GSI-responsive and GSI-resistant cell lines treated with Compound E identifies differential resopnses to GSI.
Publication Title
Mutational loss of PTEN induces resistance to NOTCH1 inhibition in T-cell leukemia.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 20 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Gain-of-function mutations in NOTCH1 are common in T-cell lymphoblastic leukemias making this receptor a promising target for drugs such as gamma-secretase inhibitors, which block a proteolytic cleavage required for NOTCH1 activation. However, the enthusiasm for these therapies has been tempered by tumor resistance and the paucity of information on the oncogenic programs regulated by oncogenic NOTCH1. Here we show that NOTCH1 regulates PTEN expression and the activity of the PI3K-AKT signaling pathway in normal and leukemic T cells. Notch signaling and the PI3K-AKT pathway synergize in vivo in a Drosophila model of Notch-induced tumorigenesis, and mutational loss of PTEN is associated with increased glycolysis and resistance to NOTCH1 inhibition in human T-ALL. These findings identify the transcriptional regulation of PTEN and the control of cellular metabolism as key elements of the oncogenic program activated by NOTCH1 and provide the basis for the design of new therapeutic strategies for T-ALL.
Publication Title
Mutational loss of PTEN induces resistance to NOTCH1 inhibition in T-cell leukemia.
Sample Metadata Fields
No sample metadata fields
View Samples- Danio rerio
- 6 Downloadable Samples
IlluminaHiSeq2500
Description
We report gene expression data for FACS sorted zebrafish mpeg1:mCherry + and mpx:EGFP + cells collected from whole embryos at 72 hours post fertilization (hpf). We also report gene expression data for the remaining, transgene negative, portion of these embryos. Overall design: ~1,000 mpeg1:mCherry+; mpx:EGFP+ transgenic embryos were homogenized, filtered, and sorted using FACS into PBS, collecting >50,000 cells for each of the three populations: mpeg1:mCherry+, mpx:EGFP+ and double negative (no double positive cells were collected as there was almost no overlap between mCherry and EGFP expression).
Publication Title
Distinct Roles for Matrix Metalloproteinases 2 and 9 in Embryonic Hematopoietic Stem Cell Emergence, Migration, and Niche Colonization.
Sample Metadata Fields
No sample metadata fields
View Samples- Arabidopsis thaliana
- 165 Downloadable Samples
- NextSeq 500
Description
A fundamental question in biology is how gene expression is regulated to give rise to a phenotype. However, transcriptional variability is rarely considered and could influence the relationship between genotype and phenotype. It is known in unicellular organisms that gene expression is often noisy rather than uniform and has been proposed to be beneficial when environmental conditions are unpredictable. However, little is known about transcriptional variability in multicellular organisms. Using transcriptomic approaches, we analysed gene expression variability over a 24 hours time-course between individual Arabidopsis thaliana plants growing in stable conditions. We identified hundreds of genes that exhibit high inter-individual variability and found that many are involved in environmental responses. We also identified factors that might facilitate gene expression variability, such as gene size, the number of transcription factors regulating a gene and the chromatin environment. These results will bring a new light into the impact of transcriptional variability in gene expression regulation in plants. Overall design: RNA-seq were generated for 14 individual seedlings for each of the 12 following time points: ZT2, ZT4, ZT6, ZT8, ZT10, ZT12 (just before dusk), ZT14, ZT16, ZT18, ZT20, ZT22 and ZT24 (just before dawn).
Publication Title
Widespread inter-individual gene expression variability in <i>Arabidopsis thaliana</i>.
Sample Metadata Fields
Specimen part, Subject, Time
View Samples- Homo sapiens
- 14 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
The transcription factor GATA6 enables self-renewal of colon adenoma stem cells by repressing BMP gene expression.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 8 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Aberrant activation of WNT signaling and loss of BMP signals represent the two main alterations leading to the initiation of colorectal cancer (CRC). Here we screen for genes required for maintaining the tumor stem cell phenotype and identify the zinc-finger transcription factor GATA6 as key regulator of the WNT and BMP pathways in CRC. GATA6 directly drives the expression of LGR5 in adenoma stem cells while it restricts BMP signaling to differentiated tumor cells. Genetic deletion of Gata6 in mouse colon adenomas increases the levels of BMP factors, which signal to block self-renewal of tumor stem cells. In human tumors, GATA6 competes with beta-catenin/TCF4 for binding to a distal regulatory region of the BMP4 locus that has been previously linked to increased susceptibility to develop CRC. Hence, GATA6 creates a permissive environment for tumor stem cell expansion by controlling the major signaling pathways that influence CRC initiation.
Publication Title
The transcription factor GATA6 enables self-renewal of colon adenoma stem cells by repressing BMP gene expression.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Aberrant activation of WNT signaling and loss of BMP signals represent the two main alterations leading to the initiation of colorectal cancer (CRC). Here we screen for genes required for maintaining the tumor stem cell phenotype and identify the zinc-finger transcription factor GATA6 as key regulator of the WNT and BMP pathways in CRC. GATA6 directly drives the expression of LGR5 in adenoma stem cells while it restricts BMP signaling to differentiated tumor cells. Genetic deletion of Gata6 in mouse colon adenomas increases the levels of BMP factors, which signal to block self-renewal of tumor stem cells. In human tumors, GATA6 competes with beta-catenin/TCF4 for binding to a distal regulatory region of the BMP4 locus that has been previously linked to increased susceptibility to develop CRC. Hence, GATA6 creates a permissive environment for tumor stem cell expansion by controlling the major signaling pathways that influence CRC initiation.
Publication Title
The transcription factor GATA6 enables self-renewal of colon adenoma stem cells by repressing BMP gene expression.
Sample Metadata Fields
Specimen part, Cell line
View Samples