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Homo sapiens
15 Downloadable Samples
Illumina HiSeq 2000, Affymetrix Human Gene 2.1 ST Array (hugene21st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
7q11.23 dosage-dependent dysregulation in human pluripotent stem cells affects transcriptional programs in disease-relevant lineages.
Sample Metadata Fields
Sex, Specimen part, Subject
View Samples- Homo sapiens
- 15 Downloadable Samples
Affymetrix Human Gene 2.1 ST Array (hugene21st)
Description
We apply the cellular reprogramming experimental paradigm to two disorders caused by symmetrical copy number variations (CNV) of 7q11.23 and displaying a striking combination of shared as well as symmetrically opposite phenotypes: Williams Beuren syndrome (WBS) and 7q microduplication syndrome (7dup). Through a uniquely large and informative cohort of transgene-free patient-derived induced pluripotent stem cells (iPSC), along with their differentiated derivatives, we find that 7q11.23 CNV disrupt transcriptional circuits in disease-relevant pathways already at the pluripotent state. These alterations are then selectively amplified upon differentiation into disease-relevant lineages, thereby establishing the value of large iPSC cohorts in the elucidation of disease-relevant developmental pathways. In addition, we functionally define the quota of transcriptional dysregulation specifically caused by dosage imbalances in GTF2I (also known as TFII-I), a transcription factor in 7q11.23 thought to play a critical role in the two conditions, which we found associated to key repressive chromatin modifiers. Finally, we created an open-access web-based platform (accessible at http://bio.ieo.eu/wbs/ ) to make accessible our multi-layered datasets and integrate contributions by the entire community working on the molecular dissection of the 7q11.23 syndromes.
Publication Title
7q11.23 dosage-dependent dysregulation in human pluripotent stem cells affects transcriptional programs in disease-relevant lineages.
Sample Metadata Fields
Sex, Specimen part, Subject
View Samples- Mus musculus
- 20 Downloadable Samples
- Affymetrix Mouse Gene 1.1 ST Array (mogene11st)
Description
The transcription factor farnesoid X receptor (FXR) governs bile acid and energy homeostasis, is involved in inflammation, and has protective functions in the liver. In the present study we investigated the effect of Fxr deficiency in mouse precision cut liver slices (PCLS) exposed to a model hepatotoxicant cyclosporin A (CsA). It was anticipated that Fxr deficiency could aggravate toxicity of CsA in PCLS and pinpoint to novel genes/processes regulated by FXR.
Publication Title
Cyclosporin A induced toxicity in mouse liver slices is only slightly aggravated by Fxr-deficiency and co-occurs with upregulation of pro-inflammatory genes and downregulation of genes involved in mitochondrial functions.
Sample Metadata Fields
No sample metadata fields
View Samples- Saccharomyces cerevisiae
- 17 Downloadable Samples
- Affymetrix Yeast Genome S98 Array (ygs98)
Description
Physiological effects of carbon dioxide and impact on genome-wide transcript profiles were analysed in chemostat cultures of Saccharomyces cerevisiae. In anaerobic, glucose-limited chemostat cultures grown at atmospheric pressure, cultivation under CO2-saturated conditions had only a marginal (<10%) impact on the biomass yield. Conversely, a 25% decrease of the biomass yield was found in aerobic, glucose-limited chemostat cultures aerated with a mixture of 79% CO2 and 21% O2. This observation indicated that respiratory metabolism is more sensitive to CO2 than fermentative metabolism. Consistent with the more pronounced physiological effects of CO2 in respiratory cultures, the number of CO2-responsive transcripts was higher in aerobic cultures than in anaerobic cultures. Many genes involved in mitochondrial functions showed a transcriptional response to elevated CO2 concentrations. This is consistent with an uncoupling effect of CO2 and/or intracellular bicarbonate on the mitochondrial inner membrane. Other transcripts that showed a significant transcriptional response to elevated CO2 included NCE103 (probably encoding carbonic anhydrase), PCK1 (encoding PEP carboxykinase) and members of the IMD gene family (encoding isozymes of inosine monophosphate dehydrogenase
Publication Title
Physiological and genome-wide transcriptional responses of Saccharomyces cerevisiae to high carbon dioxide concentrations.
Sample Metadata Fields
No sample metadata fields
View Samples- Saccharomyces cerevisiae
- 12 Downloadable Samples
- Affymetrix Yeast Genome S98 Array (ygs98)
Description
Raw expression values (CHP data) for transcriptional profiling of the response of Saccharomyces cerevisiae to challenges with lactic acid at pH 3 and pH 5.
Publication Title
Physiological and transcriptional responses to high concentrations of lactic acid in anaerobic chemostat cultures of Saccharomyces cerevisiae.
Sample Metadata Fields
No sample metadata fields
View Samples- Saccharomyces cerevisiae
- 11 Downloadable Samples
- Affymetrix Yeast Genome S98 Array (ygs98)
Description
The present study aims to explore the role of Rim15 in both physiology and genome wide expression in S. cerevisiae under severe caloric restriction. Non-growing but metabolically active cultures of S. cerevisiae are of major interest for application in industry and as model systems for aging in higher eukaryotes. Using retentostat cultivations, almost non-growing but metabolic active cultures can be obtained resulting from the severe caloric restriction, yet not starvation, yeast experiences. Rim15 plays an important role in several nutrient sensing pathways and is involved in activating stress response and glycogen accumulation upon nutrient shortage. To investigate the role of Rim15 in the extreme robustness and glycogen accumulation of anaerobic retentostat cultures, a rim15 deletion strain is compared with its parental strain under anaerobic calorie restriction on both physiology and transcriptome.
Publication Title
To divide or not to divide: a key role of Rim15 in calorie-restricted yeast cultures.
Sample Metadata Fields
No sample metadata fields
View Samples- Saccharomyces cerevisiae
- 10 Downloadable Samples
- Affymetrix Yeast Genome S98 Array (ygs98)
Description
The pattern of gene transcription in Saccharomyces cerevisiae is strongly affected by the presence of glucose. An increased activity of protein kinase A (PKA), triggered by a rise in the intracellular concentration of cAMP, can account for many of the effects of glucose on transcription. To investigate the requirement of PKA for glucose control of gene expression, we have analyzed global transcription in strains devoid of PKA activity. In S. cerevisiae three genes, TPK1, TPK2, TPK3, encode catalytic subunits of PKA and the triple mutant tpk1 tpk2 tpk3 is unviable. We have worked, therefore, with two strains, tpk1 tpk2 tpk3 yak1 and tpk1 tpk2 tpk3 msn2 msn4, that bear suppressor mutations,. We have identified different classes of genes that can be induced, or repressed, by glucose in the absence of PKA. Among these genes, some are also controlled by a redundant signalling pathway involving PKA activation, while others do not respond to an increase in cAMP concentration. On the other hand, among genes which do not respond to glucose in the absence of PKA, some show a full response to increased cAMP levels, even in the absence of glucose, while others appear to require the cooperation of different signalling pathways.
Publication Title
Transcriptional responses to glucose in Saccharomyces cerevisiae strains lacking a functional protein kinase A.
Sample Metadata Fields
Treatment, Time
View Samples- Saccharomyces cerevisiae
- 3 Downloadable Samples
- Affymetrix Yeast Genome S98 Array (ygs98)
Description
Prolonged cultivation (>25 generations) of Saccharomyces cerevisiae in aerobic, maltose-limited chemostat cultures led to profound physiological changes. Maltose hypersensitivity was observed when cells from prolonged cultivations were suddenly exposed to excess maltose. This substrate hypersensitivity was evident from massive cell lysis and loss of viability. During prolonged cultivation at a fixed specific growth rate, the affinity for the growth-limiting nutrient (i.e., maltose) increased, as evident from a decreasing residual maltose concentration. Furthermore, the capacity of maltose-dependent proton uptake increased up to 2.5-fold during prolonged cultivation. Genome-wide transcriptome analysis showed that the increased maltose transport capacity was not primarily due to increased transcript levels of maltose-permease genes upon prolonged cultivation. We propose that selection for improved substrate affinity (ratio of maximum substrate consumption rate and substrate saturation constant) in maltose-limited cultures leads to selection for cells with an increased capacity for maltose uptake. At the same time, the accumulative nature of maltose-proton symport in S. cerevisiae leads to unrestricted uptake when maltose-adapted cells are exposed to a substrate excess. These changes were retained after isolation of individual cell lines from the chemostat cultures and nonselective cultivation, indicating that mutations were involved. The observed trade-off between substrate affinity and substrate tolerance may be relevant for metabolic engineering and strain selection for utilization of substrates that are taken up by proton symport.
Publication Title
Prolonged maltose-limited cultivation of Saccharomyces cerevisiae selects for cells with improved maltose affinity and hypersensitivity.
Sample Metadata Fields
No sample metadata fields
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GSE69408- Homo sapiens
- 39 Downloadable Samples
- Affymetrix Human Gene 1.1 ST Array (hugene11st)
Description
Aging within the human hematopoietic system associates with increased incidence of anemia and myeloid neoplasms, decreased bone marrow (BM) cellularity and reduced adaptive immune responses. Similar phenotypes have been observed in mice and shown, at least in part, to involve hematopoietic stem cells (HSCs). However, evidence supporting such an association within human hematopoiesis is still sparse and prompted us to detail characteristics of human hematopoietic stem and progenitor cells throughout ontogeny.
Publication Title
Human and Murine Hematopoietic Stem Cell Aging Is Associated with Functional Impairments and Intrinsic Megakaryocytic/Erythroid Bias.
Sample Metadata Fields
Specimen part
View Samples- Saccharomyces cerevisiae
- 22 Downloadable Samples
- Affymetrix Yeast Genome S98 Array (ygs98)
Description
Despite the scientific and applied interest in anaerobic metabolism of Saccharomyces cerevisiae, not all genes whose transcription is up-regulated under anaerobic conditions have yet been linked to known transcription factors. Experiments with a reporter construct in which the promoter of the anaerobically up-regulated TIR1 gene was fused to LacZ revealed a complete loss of anaerobic up-regulation in a snf7 mutant. Anaerobic up-regulation was restored by expression of a truncated allele of RIM101 that encodes for a constitutively active Rim101p transcription factor. Analysis of LacZ expression in several deletion mutants confirmed that the effect of Snf7p on anaerobic up-regulation of TIR1 involved Rim101p and did not require a functional multi-vesicular body sorting pathway (in which Snf7p also participates). Transcriptome analysis in anaerobic chemostat cultures revealed that 26 additional genes exhibited a Snf7p/Rim101p dependent anaerobic up-regulation. Since, in its activated form, Rim101p is generally known as a transcriptional repressor, its role in anaerobic up regulation of TIR1 and other anaerobic yeast genes must involve additional factors. Further studies with deletion mutants in NRG1, NRG2 and SMP1, which were previously shown to be regulated by Rim101p, showed that these genes were not involved in the regulation of TIR1. However, the aerobic repression mechanism of TIR1 involved the general repressor Ssn6p-Tup1p complex. The physiological relevance of Snf7p/Rim101p-mediated transcriptional up-regulation of several genes in anaerobic yeast cultures was evident from reduced growth of a snf7 under anaerobic conditions.
Publication Title
Involvement of Snf7p and Rim101p in the transcriptional regulation of TIR1 and other anaerobically upregulated genes in Saccharomyces cerevisiae.
Sample Metadata Fields
No sample metadata fields
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