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Homo sapiens
28 Downloadable Samples
Illumina HiSeq 2500
Description
Pluripotent stem cells can switch their unique metabolic requirements to facilitate cellular changes but it is not clear if adult stem cells utilize metabolism in a similar manner. Here we studied the metabolism of a human adult stem cell: dental pulp stem cells (DPSCs). The dental pulp from third molars of a diverse patient group was surgically extracted, generating cells that had a high percentage of mesenchymal stem cell markers CD29, CD44, CD146 and Stro1 and had the ability to differentiate into osteogenic and adipogenic lineages. Through RNA seq analysis we identified homeobox protein, Barx1, as a marker for DPSCs. Furthermore, using high throughput proteomic analysis we identified markers for DPSC populations with accelerated replicative senescence. In particular, we show that the transforming growth factor-beta (TGF-ß) pathway and the proteins associated with muscle contraction are upregulated in rapid aging DPSCs, indicating a loss of stem cell characteristics and spontaneous initiation of terminal differentiation. Importantly, using metabolic flux analysis, we identified a metabolic signature for the rapid aging DPSCs. This metabolic signature can be used to predict the onset of replicative senescence phenotypes. Hence, the present study identifies Barx1 as a DPSCs marker and dissects the first predictive metabolic signature for DPSCs aging. Overall design: We did RNA-seq of dental pulp stem cells (DPSC) using our own approach (ID# 29, 43, 44, 45), as well as commercial DPSC and mesenchymal stem cells (MCS) from Lonza.
Publication Title
Metabolism as an early predictor of DPSCs aging.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 4 Downloadable Samples
- Illumina HiSeq 2500
Description
Although human pluripotent stem cells-derived cardiomyocytes (hPSC-CMs) have emerged as a novel platform for heart regeneration, disease modeling, and drug screening, their immaturity significantly hinders their application. A hallmark of postnatal cardiomyocyte maturation is the metabolic substrate switch from glucose to fatty acids. We hypothesized that fatty acid supplementation would enhance hPSC-CM maturation. Fatty acid treatment induces cardiomyocyte hypertrophy and significantly increases cardiomyocyte force production. The improvement in force generation is accompanied by enhanced calcium transient peak height and kinetics, and by increased action potential upstroke velocity. Fatty acids enhance mitochondrial respiratory reserve capacity. RNA sequencing showed fatty acid treatment upregulates genes involved in fatty acid ß-oxidation and downregulates genes in lipid synthesis. Signal pathway analyses reveal that fatty acid treatment results in phosphorylation of multiple intracellular kinases. Thus, fatty acids increase human cardiomyocyte hypertrophy, force generation, calcium dynamics, action potential upstroke velocity, and oxidative capacity. This enhanced maturation should facilitate hPSC-CMs usage for cell therapy, disease modeling, and drug/toxicity screens. Overall design: We did RNA-seq of hPSC-CM culture in control and fatty acid media, with two biological replicates per condition
Publication Title
Fatty Acids Enhance the Maturation of Cardiomyocytes Derived from Human Pluripotent Stem Cells.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 8 Downloadable Samples
- Illumina HiSeq 2500
Description
We generated primary cultures from renal cell carcinoma and matched normal primary kidney cortex tubule cell cultures from 3 patients. Early passage cultures of these two cell types were subjected to chromatin accessibility profiling (DNase-seq) and gene expression profiling (RNA-seq). Studying these paired and patient-matched controlled data sets will shed light on the epigenomic changes that underlie transformation of kidney tubules into malignant cancers. Overall design: Paired DNase-seq and RNA-seq data sets from 2 different primary human kidney cell types (normal and cancer) Note from submitter: The HIM23 samples have a more narrow consent and their raw data will be submitted to dbGaP.
Publication Title
Integrated epigenomic profiling reveals endogenous retrovirus reactivation in renal cell carcinoma.
Sample Metadata Fields
Sex, Age, Cell line, Subject
View Samples- Homo sapiens
- 4 Downloadable Samples
Description
The polycomb repressive complex 2 (PRC2) histone methyl-transferase plays a central role in epigenetic regulation in development and in cancer, and hence to interrogate its role in a specific developmental transition, methods are needed for disrupting function of the complex with high temporal and spatial precision. The catalytic and substrate recognition functions of PRC2 are coupled by binding of the N-terminal helix of the Ezh2 methylase to an extended groove on the EED trimethyl lysine binding subunit. Disrupting PRC2 function can in principle be achieved by blocking this single interaction, but there are few approaches for blocking specific protein-protein interactions in living cells and organisms. Here, we describe the computational design of proteins that bind to the EZH2 interaction site on EED with sub-nanomolar affinity in vitro and form tight and specific complexes with EED in living cells. Induction of the EED binding proteins abolishes H3K27 methylation in human embryonic stem cells (hESC) and at all but the earliest stage blocks self-renewal, pinpointing the first critical repressive H3K27me3 marks in development. Overall design: 1 biological sample were isolated from naïve hESC cell line Elf1 and Elf1 expressing EED binder 22.2. RNA-seq and ChIP-seq (H3K27me3) was performed for each sample.
Publication Title
First critical repressive H3K27me3 marks in embryonic stem cells identified using designed protein inhibitor.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 6 Downloadable Samples
Description
We analyzed chromatin dynamics and transcriptional activity of human embryonic stem cell (hESC)-derived cardiac progenitor cells (CPCs) and KDR+/CD34+ endothelial cells generated from cardiogenic or hemogenic mesoderm. Using an unbiased algorithm to hierarchically rank genes modulated at the level of chromatin and transcription, we identified novel candidate regulators of mesodermal lineage determination. HOPX, a non-DNA binding homeodomain protein, was identified as a candidate regulator of blood-forming endothelial cells. We used HOPX reporter and knockout hESCs, as well as hopx loss of function studies in zebrafish, to show the requirement of HOPX in vivo and in vitro in hemato-endothelial lineage specification. Loss of HOPX does not impact endothelial fate specification but markedly reduces primitive hematopoiesis acting at least in part through suppression of Wnt/ß-catenin signaling. Single cell RNA-seq data during mouse hematopoietic development in vivo confirm a role for HOPX in hematopoietic fate. Taken together, we show that HOPX is a novel regulator of hemato-endothelial fate specification in vitro and in vivo that functionally regulates Wnt signaling to modulate primitive hematopoiesis. Overall design: 2 biological replicates were isolated from cardiac progenitor cells (CPCs) and endothelial populations derived from cardiogenic mesoderm (C-ECs) and hemogenic mesoderm (H-ECs). RNA-seq and ChIP-seq (H3K4me3 and H3K27me3) was performed for each replicate.
Publication Title
Single-Cell Transcriptomic Analysis of Cardiac Differentiation from Human PSCs Reveals HOPX-Dependent Cardiomyocyte Maturation.
Sample Metadata Fields
No sample metadata fields
View Samples- Saccharomyces cerevisiae
- 15 Downloadable Samples
Affymetrix Yeast Genome S98 Array (ygs98)
Description
In the present study transcriptome and proteome of recombinant, xylose-utilising S. cerevisiae grown in aerobic batch cultures on xylose were compared with glucose-grown cells both in glucose repressed and derepressed states. The aim was to study at genome-wide level how signalling and carbon catabolite repression differed in cells grown on either glucose or xylose. The more detailed knowledge about is xylose sensed as a fermentable carbon source, capable of catabolite repression like glucose, or is it rather recognised as a non-fermentable carbon source is important in achieving understanding for further engineering this yeast for more efficient anaerobic fermentation of xylose.
Publication Title
Regulation of xylose metabolism in recombinant Saccharomyces cerevisiae.
Sample Metadata Fields
No sample metadata fields
View Samples- Saccharomyces cerevisiae
- 26 Downloadable Samples
- Affymetrix Yeast Genome 2.0 Array (yeast2)
Description
In industrial fermentations of Saccharomyces cerevisiae, transient changes in oxygen concentration commonly occur and it is important to understand the behaviour of cells during these changes. Saccharomyces cerevisiae CEN.PK113-1A was grown in glucose-limited chemostat culture with 1.0% and 20.9% O2 in the inlet gas (D= 0.10 /h, pH5, 30C). After steady state was achieved, oxygen was replaced with nitrogen and cultures were followed until new steady state was achieved. The overall responses to anaerobic conditions of cells initially in different conditions were very similar. Independent of initial culture conditions, transient downregulation of genes related to growth and cell proliferation, mitochondrial translation and protein import, and sulphate assimilation was seen. In addition, transient or permanent upregulation of genes related to protein degradation, and phosphate and amino acid uptake was observed in all cultures. However, only in the initially oxygen-limited cultures was a transient upregulation of genes related to fatty acid oxidation, peroxisomal biogenesis, oxidative phosphorylation, TCA cycle, response to oxidative stress, and pentose phosphate pathway observed. Furthermore, from the initially oxygen-limited conditions, a rapid response around the metabolites of upper glycolysis and the pentose phosphate pathway was seen, while from the initially fully aerobic conditions, a slower response around the pathways for utilisation of respiratory carbon sources was observed.
Publication Title
Transcriptional responses of Saccharomyces cerevisiae to shift from respiratory and respirofermentative to fully fermentative metabolism.
Sample Metadata Fields
Time
View Samples- Mus musculus
- 22 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Proteinases play a pivotal role in wound healing by degrading molecular barriers, regulating cell-matrix interactions and availability of bioactive molecules. Matrix metalloproteinase-13 (MMP-13, collagenase-3) is a wide spectrum proteinase. Its expression and function is linked to the growth and invasion of many epithelial cancers such as squamous cell carcinoma. Moreover, the physiologic expression of MMP-13 is associated e.g. to scarless healing of human fetal skin and adult gingival wounds. While MMP-13 is not found in the normally healing skin wounds in human adults, it is expressed in mouse skin during wound healing. Thus, mouse wound healing models can be utilized for studying the role of MMP-13 in the events of wound healing. As the processes such as the migration and proliferation of keratinocytes, angiogenesis, inflammation and activation of fibroblasts are components of wound repair as well as of cancer, many results received from wound healing studies are also adaptable to cancer research.
Publication Title
MMP-13 regulates growth of wound granulation tissue and modulates gene expression signatures involved in inflammation, proteolysis, and cell viability.
Sample Metadata Fields
Time
View Samples
GSE85998- Mus musculus
- 47 Downloadable Samples
- Affymetrix Mouse Gene 2.1 ST Array (mogene21st)
Description
Livers from 15 month old mice mainatined on one of 25 different diets varying in protein, carbohydrate, fat (P,C,F) and energy content were analysed. Energy content was categorised as low (8kJ/g), medium (13kJ/g) or high (17kJ/g) Mice were placed on diet from 3 weeks of age and a subset culled for various analyses. The rest of the cohort was allowed to live out their natural life to assess lifespan.
Publication Title
Defining the Nutritional and Metabolic Context of FGF21 Using the Geometric Framework.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 25 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Asbestos has been shown to cause chromosomal damage and DNA aberrations. The fiber is associated with many different lung diseases such as asbestosis, malignant mesothelioma, and lung cancer, but the disease-related processes are still largely unknown. Our aim was to identify specific gene expression profiles by using Affymetrix arrays, in human cell lines A549, Beas-2B, and MeT5A exposed to asbestos in a time-dependent manner. The hybridization data was analyzed using an algorithm specifically designed for clustering short time series expression data, a canonical correlation analysis (CCA) for identifying correlations between the cell lines, and a Gene Ontology (GO) analysis method for the identification of enriched differentially expressed biological processes.
Publication Title
Gene expression profiles in asbestos-exposed epithelial and mesothelial lung cell lines.
Sample Metadata Fields
No sample metadata fields
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