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GSE85959
Mus musculus
23 Downloadable Samples
Illumina MouseRef-8 v2.0 expression beadchip
Description
Basic helix loop helix enhancer 40 (Bhlhe40) is a transcription factor expressed in rodent hippocampus, however, its role in neuronal function is not well understood. Here, we used Bhlhe40 null mice on a congenic C57Bl6/J background (Bhlhe40 KO) to investigate the impact of Bhlhe40 on neuronal excitability and synaptic plasticity. A whole genome expression array predicted that Bhlhe40 KO mice have up-regulated insulin-related pathways and down-regulated neuronal signaling-related pathways in the hippocampus. We validated that insulin degrading enzyme mRNA (Ide) and IDE protein are significantly downregulated in Bhlhe40 KO hippocampi. No significant difference was observed in hippocampal insulin levels. In hippocampal slices, we found CA1 neurons have increased miniature excitatory post-synaptic current (mEPSC) amplitude and decreased inhibitory post-synaptic current (IPSC) amplitude, indicating hyper-excitability in CA1 neurons in Bhlhe40 KO mice. At CA1 synapses, we found a reduction in long term potentiation (LTP) and long term depression (LTD), indicating an impairment in hippocampal synaptic plasticity in Bhlhe40 KO hippocampal slices. Bhlhe40 KO mice displayed no difference in seizure response to the convulsant kainic acid (KA) relative to controls. We found that while Bhlhe40 KO mice have decreased exploratory behavior they do not display alterations in spatial learning and memory. Together this suggests that Bhlhe40 plays a role in modulating neuronal excitability and synaptic plasticity ex vivo, however, Bhlhe40 alone does not play a significant role in seizure susceptibility and learning and memory in vivo. In addition, based on the reduction in IDE protein levels in these mice, there may be dysregulation of other known IDE substrates, namely insulin growth factor (Igf)-1, Igf-2, and Amyloid beta (A).
Publication Title
Mice lacking the transcriptional regulator Bhlhe40 have enhanced neuronal excitability and impaired synaptic plasticity in the hippocampus.
Sample Metadata Fields
Sex, Specimen part
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
- 16 Downloadable Samples
- Affymetrix Yeast Genome S98 Array (ygs98)
Description
Sucrose is a major carbon source for industrial bioethanol production by Saccharomyces cerevisiae. In yeasts, two modes of sucrose metabolism occur: (i) extracellular hydrolysis by invertase, followed by uptake and metabolism of glucose and fructose, and (ii) uptake via sucrose-H+ symport followed by intracellular hydrolysis and metabolism. Although alternative start codons in the SUC2 gene enable synthesis of extracellular and intracellular invertase isoforms, sucrose hydrolysis in S. cerevisiae predominantly occurs extracellularly. In anaerobic cultures, intracellular hydrolysis theoretically enables a 9 % higher ethanol yield than extracellular hydrolysis, due to energy costs of sucrose-proton symport. This prediction was tested by engineering the promoter and 5 coding sequences of SUC2, resulting in relocation of invertase to the cytosol. In anaerobic sucrose-limited chemostats, this iSUC2-strain showed an only 4% increased ethanol yield and high residual sucrose concentrations indicated suboptimal sucrose-transport kinetics. To improve sucrose-uptake affinity, it was subjected to 95 generations of anaerobic, sucrose-limited chemostat cultivation, resulting in a 20-fold decrease of residual sucrose concentrations and a 10-fold increase of the sucrose-transport capacity. A single-cell isolate showed an 11 % higher ethanol yield on sucrose in chemostat and batch cultures than an isogenic SUC2 reference strain, while transcriptome analysis revealed elevated expression of AGT1, encoding a disaccharide-proton symporter, and other maltose-related genes. Deletion of AGT1, which had been duplicated during laboratory evolution, restored the growth characteristics of the unevolved iSUC2 strain. This study demonstrates that engineering the topology of sucrose metabolism is an attractive strategy to improve ethanol yields in industrial processes.
Publication Title
Increasing free-energy (ATP) conservation in maltose-grown Saccharomyces cerevisiae by expression of a heterologous maltose phosphorylase.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 12 Downloadable Samples
- Affymetrix Human Genome U219 Array (hgu219)
Description
As a transcription factor, SOX7 suppresses cancer development. However, only a few genes were demonstrated as SOX7-activated targets in cancer-irrelevant contexts. We used microarray chips to determine SOX7 target genes in breast cancer cells and discovered multiple signaling pathways altered by ectopic SOX7. We also investigated several genes for their roles in SOX7-mediated tumor suppression. Our study innovatively revealed SOX7 target gene profile in a cancer-relevant context and identified several SOX7-repressed target genes.
Publication Title
SOX7 Target Genes and Their Contribution to Its Tumor Suppressive Function.
Sample Metadata Fields
Sex, Specimen part, Cell line
View Samples- Homo sapiens
- 12 Downloadable Samples
- Affymetrix Clariom S Human array (clariomshuman)
Description
The major antioxidant glutathione (GSH) protects cancer cells from oxidative damage leading to ferroptosis, an iron-dependent cell death. Therapy-resistant cancer cells often manifest high expression of the cystine-glutamate antiporter subunit xCT which enhances cystine uptake leading to GSH synthesis and thereby survive oxidative damage and ferroptosis. The use of GSH-depleting agents including xCT inhibitors might thus be expected to enhance the efficacy of cancer therapy. On the other hand, the efficacy of xCT-targeted therapy depends on the cellular metabolism affecting antioxidant system in cancer cells and metabolic reprograming might reduce the efficacy of cancer therapy using xCT inhibitors. Recently, to overcome the resistance to xCT-targeted therapy, we performed a library screening and identified an oral anesthetics dyclonine (DYC) as a sensitizing drug for xCT inhibitor sulfasalazine (SSZ). However, DYC is a local anesthetic and might not suitable for the systemic administration combined with SSZ in a clinical setting. In this study, we identified a vasodilator oxyfedrine (OXY) which is clinically used in systemic administration also acts as a sensitizing drug to GSH-depleting agents in multiple type of cancer cells. OXY and DYC share the motif required for the covalent inhibition of aldehyde dehydrogenases (ALDHs), and combined treatment with OXY and SSZ induced the accumulation of cytotoxic aldehyde 4-hydroxynonenal (4-HNE) and induce cell death in SSZ-resistant cancer cells. Furthermore, we found that OXY sensitizes cancer cells to radiation therapy which decreases intracellular GSH content. Our findings establish a rationale for repurposing of OXY as a sensitizing drug for xCT-targeted cancer therapy.
Publication Title
Vasodilator oxyfedrine inhibits aldehyde metabolism and thereby sensitizes cancer cells to xCT-targeted therapy.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Tropomodulins (Tmods) cap the pointed ends of actin filaments in erythroid and nonerythoid cell types. Targeted deletion of mouse Tmod3 leads to embryonic lethality at E14.5-E18.5, with anemia due to defects in definitive erythropoiesis in the fetal liver. BFU-E and CFU-E colony numbers are greatly reduced, indicating defects in progenitor populations. Flow-cytometry of fetal liver erythroblasts shows late stage populations are also decreased, including reduced percentages of enucleated cells. AnnexinV staining indicates increased apoptosis of Tmod3-/- erythroblasts, and cell cycle analysis reveals that there are more Ter119hi cells in S-phase in Tmod3-/- embryos. Notably, enucleating Tmod3-/- erythroblasts are still in the process of proliferation, suggesting impaired cell cycle exit during terminal differentiation. Tmod3-/- late erythroblasts often exhibit multi-lobular nuclear morphologies and aberrant F-actin assembly during enucleation. Furthermore, native erythroblastic island formation was impaired in Tmod3-/- fetal livers, with Tmod3 required in both erythroblasts and macrophages. In conclusion, disruption of Tmod3 leads to impaired definitive erythropoiesis, due to reduced progenitors, impaired erythroblastic island formation, and defective erythroblast cell cycle progression and enucleation. Tmod3-mediated actin remodeling may be required for erythroblast-macrophage adhesion, coordination of cell cycle with differentiation, and F-actin assembly and remodeling during erythroblast enucleation.
Publication Title
Tropomodulin3-null mice are embryonic lethal with anemia due to impaired erythroid terminal differentiation in the fetal liver.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 9 Downloadable Samples
- Affymetrix Human Genome U219 Array (hgu219)
Description
Gene expression profiling reveals a potential role of WOL in differentiation of CD34+ cells towards erythropoiesis
Publication Title
Comprehensive transcriptome analysis of erythroid differentiation potential of olive leaf in haematopoietic stem cells.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 13 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
A major goal in prostate stem cell biology is to identify genes, pathways, or networks that control self-renewal and multilineage differentiation. We hypothesize that 1,25 dihydroxyvitamin D3 can induce differentiation of prostatic progenitor/stem cells, thus serving as an in vitro model with which to study the molecular mechanisms of stem cell differentiation by 1,25 dihydroxyvitamin D3. 1,25 dihydroxyvitamin D3 elicits its effects primarily through transcriptional regulation of genes, so microarray studies were used to gain insight into the cellular response to 1,25 dihydroxyvitamin D3.
Publication Title
Interleukin-1α mediates the antiproliferative effects of 1,25-dihydroxyvitamin D3 in prostate progenitor/stem cells.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 2 Downloadable Samples
IlluminaHiSeq2500
Description
Diploidy is a fundamental genetic feature in mammals, in which haploid cells normally arise only as post-meiotic germ cells that serve to insure a diploid genome upon fertilization. Gamete manipulation has yielded haploid embryonic stem (ES) cells from several mammalian species, but as of yet not from humans. Here we analyzed a large collection of human parthenogenetic ES cell lines originating from haploid oocytes, leading to the successful isolation and maintenance of human ES cell lines with a normal haploid karyotype. Haploid human ES cells exhibited typical pluripotent stem cell characteristics such as self-renewal capacity and a pluripotency-specific molecular signature. Although haploid human ES cells resembled their diploid counterparts, they also displayed distinct properties including differential regulation of X chromosome inactivation and genes involved in oxidative phosphorylation, alongside reduction in absolute gene expression levels and cell size. Intriguingly, we found that a haploid genome is compatible not only with the undifferentiated pluripotent state, but also with differentiated somatic fates representing all three embryonic germ layers, despite a persistent dosage imbalance between the autosomes and X chromosome. We expect that haploid human ES cells will provide novel means for studying human functional genomics, development and evolution. Overall design: RNA sequencing analysis was performed on a total of 2 samples of in vitro fertilization (IVF) control embryonic stem cell lines.
Publication Title
Derivation and differentiation of haploid human embryonic stem cells.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 2 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Diploidy is a fundamental genetic feature in mammals, in which haploid cells normally arise only as post-meiotic germ cells that serve to insure a diploid genome upon fertilization. Gamete manipulation has yielded haploid embryonic stem (ES) cells from several mammalian species, but as of yet not from humans. Here we analyzed a large collection of human parthenogenetic ES cell lines originating from haploid oocytes, leading to the successful isolation and maintenance of human ES cell lines with a normal haploid karyotype. Haploid human ES cells exhibited typical pluripotent stem cell characteristics such as self-renewal capacity and a pluripotency-specific molecular signature. Although haploid human ES cells resembled their diploid counterparts, they also displayed distinct properties including differential regulation of X chromosome inactivation and genes involved in oxidative phosphorylation, alongside reduction in absolute gene expression levels and cell size. Intriguingly, we found that a haploid genome is compatible not only with the undifferentiated pluripotent state, but also with differentiated somatic fates representing all three embryonic germ layers, despite a persistent dosage imbalance between the autosomes and X chromosome. We expect that haploid human ES cells will provide novel means for studying human functional genomics, development and evolution.
Publication Title
Derivation and differentiation of haploid human embryonic stem cells.
Sample Metadata Fields
Specimen part, Cell line
View Samples