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Homo sapiens
6 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The tetracycline antibiotics are widely used in biomedical research as mediators of inducible gene expression systems. Despite many known effects of tetracyclines on mammalian cells -- including inhibition of the mitochondrial ribosome -- there have been few reports on potential off-target effects at concentrations commonly used in inducible systems. Here, we report that in human cell lines, commonly used concentrations of doxycycline change gene expression patterns and concomitantly shift metabolism towards a more glycolytic phenotype, evidenced by increased lactate secretion and reduced oxygen consumption. We also show that these concentrations are sufficient to slow proliferation and alter cell cycle progression in vitro. These findings suggest that researchers using doxycycline in inducible expression systems should design appropriate controls to account for potential confounding effects of the drug on cellular metabolism.
Publication Title
Doxycycline alters metabolism and proliferation of human cell lines.
Sample Metadata Fields
Specimen part, Cell line, Treatment
View Samples- Homo sapiens
- 24 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The balance between glycolytic and oxidative metabolism shifts during differentiation of human embryonic stem cells (hESCs) and during reprogramming of somatic cells into pluripotent stem cells. However the contribution of glycolytic metabolism to various stages of pluripotency is not well understood. Additionally, few tools have been developed that modulate pluripotent stem cell glycolytic metabolism to influence self-renewal or differentiation. Here we show that the degree of human pluripotency is associated with glycolytic rate, whereby naive hESCs exhibit higher glycolytic flux, increased MYC transcriptional activity, and elevated nuclear N-MYC levels relative to primed hESCs. Consistently, the inner cell mass of human blastocysts also exhibits increased MYC transcriptional activity relative to primed hESCs and elevated nuclear N-MYC levels. Expression of the lactate transporter, monocarboxylate transporter 1 (MCT1), is strongly associated with the pluripotent state, and reduction of glycolysis using a small molecule inhibitor towards MCT1 decreases self-renewal of nave hESCs and feeder-free cultured primed hESCs, but not that of primed hESCs grown in feeder-supported conditions. Lastly, reduction of glycolytic metabolism via MCT1 inhibition in feeder-free primed hESCs enhances neural lineage specification. These findings validate the association between glycolytic metabolism and pluripotency, reveal differences in the glucose metabolism of feeder- versus feeder-free cultured hESCs, and show that pharmacologic regulation of glycolysis can influence self-renewal and initial cell fate specification of human pluripotent stem cells.
Publication Title
Glycolytic Metabolism Plays a Functional Role in Regulating Human Pluripotent Stem Cell State.
Sample Metadata Fields
Cell line, Treatment
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Adenovirus infection leads to increased glycolytic metabolism in host cells. Expression of a single gene product encoded within the E4 early transcription region, E4ORF1, is sufficient to promote increased glycolytic flux in cultured epithelial cells.
Publication Title
Adenovirus E4ORF1-induced MYC activation promotes host cell anabolic glucose metabolism and virus replication.
Sample Metadata Fields
Cell line
View Samples
SRP044781- Danio rerio
- 12 Downloadable Samples
IlluminaHiSeq2000
Description
Transcriptome analysis of 12 zebrafish tissues
Publication Title
Gene evolution and gene expression after whole genome duplication in fish: the PhyloFish database.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 9 Downloadable Samples
- Illumina HiSeq 2000
Description
We analyzed the global transcriptome signature over the time course of the cardiac differentiation from hESC by RNA-seq. We characterized the genome-wide transcriptome profile of 5 distinct stages; undifferentiated hESC (day 0), mesodermal precursor stage (hMP, day 2), cardiac progenitor stage (hCP, day 5), immature cardiomyocyte (hCM14) and hESC-CMS differentiated for 14 additional days (hCM28). While the stem cell signature decreases over the five stages, the signatures associated with heart and smooth muscle development increase, indicating the efficient cardiac differentiation of our protocol. Overall design: Five different temporal samples, two replicates for only first four samples day 0 through day 15
Publication Title
Glucose inhibits cardiac muscle maturation through nucleotide biosynthesis.
Sample Metadata Fields
Specimen part, Subject
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Ppp2r1afl/fl mouse bone marrow pre-B cells were transduced with an BCR-ABL1 vector. The BCR-ABL1 transduced Ppp2r1afl/fl pre-B cells were then transduced with an empty vector (EV), or a Cre vector for Cre-mediated PP2A deletion. Effect of PP2A deletion in the BCR-ABL1 pre-B cells were studied by Affymetrix GeneChip Mouse Genome ST1.0 Array
Publication Title
B-Cell-Specific Diversion of Glucose Carbon Utilization Reveals a Unique Vulnerability in B Cell Malignancies.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 24 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Many cancers rely on glycolytic metabolism to fuel rapid proliferation. This has spurred interest in designing drugs that target tumor glycolysis such as AZD3965, a small molecule inhibitor of Monocarboxylate Transporter 1 (MCT1) currently undergoing Phase I evaluation for cancer treatment. Since MCT1 mediates proton-linked transport of monocarboxylates such as lactate and pyruvate across the plasma membrane (Halestrap and Meredith, 2004), AZD3965 is thought to block tumor growth through disruption of lactate transport and glycolysis. Here we show that MCT1 inhibition impairs proliferation of glycolytic breast cancer cells that express MCT4 via disruption of pyruvate rather than lactate export. We found that MCT1 expression is elevated in glycolytic breast tumors and cell lines as well as in malignant breast and lung tissues. High MCT1 expression predicts poor prognosis in breast and lung cancer patients. Stable knockdown and AZD3965-mediated inhibition of MCT1 promote oxidative metabolism. Acute inhibition of MCT1 reduces pyruvate export rate but does not consistently alter lactate transport or glycolytic flux in breast cancer cells that also express MCT4. Despite the lack of glycolysis impairment, MCT1 loss-of-function decreases breast cancer cell proliferation and blocks growth of mammary fat pad xenograft tumors. Our data suggest that MCT1 expression is elevated in glycolytic cancers to promote pyruvate export, which when inhibited enhances oxidative metabolism and reduces proliferation. This study presents an alternative molecular consequence of MCT1 inhibitors that further supports their use as anti-cancer therapeutics.
Publication Title
MCT1 Modulates Cancer Cell Pyruvate Export and Growth of Tumors that Co-express MCT1 and MCT4.
Sample Metadata Fields
Cell line, Treatment
View Samples- Homo sapiens
- 23 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Tumour hypoxia exhibits a highly dynamic spatial and temporal distribution and is associated with increased malignancy and poor prognosis.
Publication Title
Two phases of disulfide bond formation have differing requirements for oxygen.
Sample Metadata Fields
Treatment
View Samples- Mus musculus
- 46 Downloadable Samples
- Ion Torrent Proton
Description
For up to 70 weeks we subcutaneuously injected two hundered p53R270HWAPCre mice to different insulin-like molecules (regular insulin, insulin glargine, insulin X10 (of AspB10), IGF1 or vehicle solution). Due to the mammary gland specific p53 mutation the p53R270HWAPCre mice will develop spontanously human like mammary gland tumors in about a year. We found that frequent injections to insulin like molecules decreased the mammary gland tumor latency time in this model. Next we mRNA seqeunced tumors to reveal the underlying mechanisms for the increased tumor progression. For the next generation experiment we isolated mRNA from 50 tumors (10 tumors of each stimulation group) and sequenced with the IonTorrent (40 mil reads, on average 100 bp reads) Overall design: RNA expression profiles of 50 mammary gland tumors were analyzed, 10 tumors per treatment group (chronic insulin, glargine, x10, IGF1 or vehicle exposure)
Publication Title
Insulin-like growth factor 1 receptor activation promotes mammary gland tumor development by increasing glycolysis and promoting biomass production.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Mus musculus
- 8 Downloadable Samples
- Illumina MouseWG-6 v2.0 expression beadchip
Description
Despite intense investigation of intrinsic and extrinsic factors that regulate pluripotency, the process of initial fate commitment of embryonic stem (ES) cells is still poorly understood. Here, we used a genome wide shRNA screen in mouse ES cells to identify genes that are essential for initiation of differentiation. Knockdown of the scaffolding protein Mek binding protein 1 (Mp1, also known as Lamtor3, Map2k1ip1) stimulated self-renewal of ES cells, blocked differentiation and promoted proliferation. Fibroblast growth factor 4 (FGF4) signaling is required for initial fate commitment of ES cells. Knockdown of Mp1 inhibited FGF4-induced differentiation but did not alter FGF4 driven proliferation. This uncoupling of differentiation and proliferation was also observed when oncogenic Ras isoforms were over expressed in ES cells. Knockdown of Mp1 redirected FGF4 signaling from differentiation towards pluripotency and upregulated the pluripotency-related genes Esrrb, Rex1, Tcl1 and Sox2.
Publication Title
A genome-wide RNAi screen in mouse embryonic stem cells identifies Mp1 as a key mediator of differentiation.
Sample Metadata Fields
Specimen part, Cell line
View Samples