Filters
Organism
Technology
Platform
GSE104175
Homo sapiens
2 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
It has been difficult to elucidate the structure of gene regulatory networks under anticancer drug treatment. Here, we developed an algorithm to highlight the hub genes that play a major role in creating the upstream and downstream relationships within a given set of differentially expressed genes. The directionality of the relationships between genes was defined using information from comprehensive collections of transcriptome profiles after gene knockdown and overexpression. As expected, among the drug-perturbed genes, our algorithm tended to derive plausible hub genes, such as transcription factors. Our validation experiments successfully showed the anticipated activity of certain hub gene in establishing the gene regulatory network that was associated with cell growth inhibition. Notably, giving such top priority to the hub gene was not achieved by ranking fold change in expression and by the conventional gene set enrichment analysis of drug-induced transcriptome data. Thus, our data-driven approach can facilitate to understand drug-induced gene regulatory networks for finding potential functional genes.
Publication Title
InDePTH: detection of hub genes for developing gene expression networks under anticancer drug treatment.
Alternate Accession IDs
Sample Metadata Fields
Cell line, Treatment
View Samples- Homo sapiens
- 8 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Inhibiting the unfolded protein response (UPR) can be a therapeutic approach, especially for targeting the tumor microenvironment. We found that compound C (also known as dorsomorphin) prevented the UPR and exerted enhanced cytotoxicity during glucose deprivation. The UPR-inhibiting activity of compound C was not associated with either AMPK or BMP signaling inhibition.
Publication Title
Compound C prevents the unfolded protein response during glucose deprivation through a mechanism independent of AMPK and BMP signaling.
Alternate Accession IDs
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 26 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Cancer cells consume large amounts of glucose because of their specific metabolic pathway. However, cancer cells exist in tumor tissue where glucose is insufficient. To survive, cancer cells likely have the mechanism to elude their glucose addiction. Here we show that functional mitochondria are essential if cancer cells are to avoid glucose addiction.
Publication Title
Mitochondria regulate the unfolded protein response leading to cancer cell survival under glucose deprivation conditions.
Alternate Accession IDs
Sample Metadata Fields
Disease, Cell line, Time
View Samples- Homo sapiens
- 40 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The unfolded protein response (UPR) is a cellular defense mechanism against glucose deprivation, a cell condition that occurs in solid tumors.
Publication Title
Chemical genomics identifies the unfolded protein response as a target for selective cancer cell killing during glucose deprivation.
Alternate Accession IDs
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 16 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Mitochondria can be involved in regulating cellular stress response to hypoxia and tumor growth, but little is known about that mechanistic relationship. Here, we show that mitochondrial deficiency severely retards tumor xenograft growth with impairing hypoxic induction of HIF-1 transcriptional activity. Using mtDNA-deficient rho0 cells, we found that HIF-1 pathway activation was comparable in slow-growing rho0 xenografts and rapid-growing parental xenografts. Interestingly, we found that ex vivo rho0 cells derived from rho0 xenografts exhibited slightly increased HIF-1alpha expression and modest HIF-1 pathway activation regardless of oxygen concentration. Surprisingly, rho0 cells, as well as parental cells treated with oxidative phosphorylation inhibitors, were unable to boost HIF-1 transcriptional activity during hypoxia, although HIF-1alpha protein levels were ordinarily increased in these cells under hypoxic conditions. These findings indicate that mitochondrial deficiency causes loss of hypoxia-induced HIF-1 transcriptional activity and thereby might lead to a constitutive HIF-1 pathway activation as a cellular adaptation mechanism in tumor microenvironment.
Publication Title
Mitochondrial deficiency impairs hypoxic induction of HIF-1 transcriptional activity and retards tumor growth.
Alternate Accession IDs
Sample Metadata Fields
Cell line
View Samples- Mus musculus
- 8 Downloadable Samples
Illumina HiSeq 2500
Description
In this study, we present a comprehensive evaluation of four RNA-Seq library preparation methods. We used three standard input protocols, the Illumina TruSeq Stranded Total RNA and TruSeq Stranded mRNA kits, and a modified NuGEN Ovation v2 kit; and an ultra-low-input RNA protocol, the TaKaRa SMARTer Ultra Low RNA Kit v3. Our evaluation of these kits included quality control measures such as overall reproducibility, 5' and 3' end-bias, and the identification of DEGs, lncRNAs, and alternatively spliced transcripts. Overall, we found that the two Illumina kits were most similar in terms of recovering DEGs, and the Illumina, modified NuGEN, and TaKaRa kits allowed identification of a similar set of DEGs. However, we also discovered that the Illumina, NuGEN and TaKaRa kits each enriched for different sets of genes. Overall design: Two mESC cell lines (biological replicates) from Zbtb24 knockout (1lox/1lox) clones are compared with two wild-type (2lox/+) clones (biological replicates) using the TaKaRa SMARTer Ultra Low RNA protocol directly on cells with no RNA preparation step. Total RNA from 100 mESCs cells and 1000 mESCs cells or approximately 1 and 10 ng RNA were used respectively.
Publication Title
Systematic evaluation of RNA-Seq preparation protocol performance.
Alternate Accession IDs
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Mus musculus
- 6 Downloadable Samples
- Illumina HiSeq 2500
Description
In this study, we present a comprehensive evaluation of four RNA-Seq library preparation methods. We used three standard input protocols, the Illumina TruSeq Stranded Total RNA and TruSeq Stranded mRNA kits, and a modified NuGEN Ovation v2 kit; and an ultra-low-input RNA protocol, the TaKaRa SMARTer Ultra Low RNA Kit v3. Our evaluation of these kits included quality control measures such as overall reproducibility, 5' and 3' end-bias, and the identification of DEGs, lncRNAs, and alternatively spliced transcripts. Overall, we found that the two Illumina kits were most similar in terms of recovering DEGs, and the Illumina, modified NuGEN, and TaKaRa kits allowed identification of a similar set of DEGs. However, we also discovered that the Illumina, NuGEN and TaKaRa kits each enriched for different sets of genes. Overall design: Three mESC cell lines (biological replicates) from Zbtb24 knockout (1lox/1lox) clones are compared with three wild-type (2lox/+) clones (biological replicates) using the TruSeq mRNA protocol.
Publication Title
Systematic evaluation of RNA-Seq preparation protocol performance.
Alternate Accession IDs
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Homo sapiens
- 18 Downloadable Samples
- Illumina human-6 v2.0 expression beadchip
Description
Global gene expression analysis of FD-iPSC and deribved neural crest cells
Publication Title
Modelling pathogenesis and treatment of familial dysautonomia using patient-specific iPSCs.
Alternate Accession IDs
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 12 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The pathways involved in hierarchical differentiation of human embryonic stem cells (hESC) into abundant and durable endothelial cells (EC) are unknown. We employed an EC-specific VE-cadherin promoter driving GFP (hVPr-GFP) to screen for factors that augmented yields of vascular-committed ECs from hESCs. In phase 1 of our approach, inhibition of TGFb, precisely at day 7 of hESC differentiation, enhanced emergence of hVPr-GFP+ ECs by 10-fold. In the second phase, TGFb-inhibition preserved proliferation and vascular identity of purified ECs, resulting in net 36-fold expansion of homogenous EC-monolayers, and allowing transcriptional profiling that revealed a unique angiogenic signature defined by the VEGFR2highId1highVE-cadherin+EphrinB2+CD133+HoxA9- phenotype. Using an Id1-YFP hESC reporter line, we showed that TGFb-inhibition sustained Id1 expression in hESC-derived ECs, which was required for increased proliferation and preservation of EC commitment. These data provide a multiphasic method for serum-free differentiation and long-term maintenance of authentic hESC-derived ECs, establishing clinical-scale generation of transplantable human ECs.
Publication Title
Expansion and maintenance of human embryonic stem cell-derived endothelial cells by TGFbeta inhibition is Id1 dependent.
Alternate Accession IDs
Sample Metadata Fields
Specimen part
View Samples- Rattus norvegicus
- 7 Downloadable Samples
- Affymetrix Rat Genome 230 2.0 Array (rat2302), UNKNOWN
Description
A study of diabetic neuropathy in dorsal root ganglia from streptozotocin-diabetic male wistar rats over the first 8 weeks of diabetes
Publication Title
Identification of changes in gene expression in dorsal root ganglia in diabetic neuropathy: correlation with functional deficits.
Alternate Accession IDs
None
Sample Metadata Fields
Sex, Age, Specimen part, Disease, Disease stage, Time
View Samples