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SRP097744
Homo sapiens
6 Downloadable Samples
Illumina HiSeq 4000
Description
We examined the ability of human NANOGNB to regulate gene expression by ectopically expressing the gene in human dermal fibroblasts. Overall design: NANOGNB and an empty control vector were transfected individually to drive ectopic expression in human dermal fibroblasts, in triplicate.
Publication Title
A sister of <i>NANOG</i> regulates genes expressed in pre-implantation human development.
Sample Metadata Fields
Subject
View Samples- Homo sapiens
- 29 Downloadable Samples
- Illumina HiSeq 4000
Description
We individually examined the ability of human ARGFX, DPRX, LEUTX, and TPRX1 to regulate gene expression by ectopically expressing these proteins in fibroblasts. Overall design: Each gene along with an empty control vector were transfected individually to drive ectopic expression in human dermal fibroblasts, in triplicate.
Publication Title
Evolutionary origin and functional divergence of totipotent cell homeobox genes in eutherian mammals.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 744 Downloadable Samples
Affymetrix Human Gene Expression Array (primeview), Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2), Affymetrix Human Genome U133A Array (hgu133a)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
NALP3 inflammasome upregulation and CASP1 cleavage of the glucocorticoid receptor cause glucocorticoid resistance in leukemia cells.
Sample Metadata Fields
Disease, Cell line, Treatment
View Samples- Homo sapiens
- 253 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
Glucocorticoids are universally used in the treatment of acute lymphoblastic leukemia (ALL), and glucocorticoid resistance in leukemia cells confers a poor prognosis. To elucidate mechanisms of glucocorticoid resistance, we determined the prednisolone sensitivity of primary leukemia cells from 444 newly diagnosed ALL patients and found significantly higher expression of caspase 1 (CASP1) and its activator NLRP3 in glucocorticoid resistant leukemia cells, due to significantly lower somatic methylation of CASP1 and NLRP3 promoters. Over-expression of CASP1 resulted in cleavage of the glucocorticoid receptor, diminished glucocorticoid-induced transcriptional response and increased glucocorticoid resistance. Knockdown or inhibition of CASP1 significantly increased glucocorticoid receptor levels and mitigated glucocorticoid resistance in CASP1 overexpressing ALL. Our findings establish a new mechanism by which the NLRP3/CASP1 inflammasome modulates cellular levels of the glucocorticoid receptor and diminishes cell sensitivity to glucocorticoids. The broad impact on glucocorticoid transcriptional response suggests this mechanism could also modify glucocorticoid effects in other diseases.
Publication Title
NALP3 inflammasome upregulation and CASP1 cleavage of the glucocorticoid receptor cause glucocorticoid resistance in leukemia cells.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 166 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2), Affymetrix Human Genome U133A Array (hgu133a)
Description
Glucocorticoids are universally used in the treatment of acute lymphoblastic leukemia (ALL), and glucocorticoid resistance in leukemia cells confers a poor prognosis. To elucidate mechanisms of glucocorticoid resistance, we determined the prednisolone sensitivity of primary leukemia cells from 444 newly diagnosed ALL patients and found significantly higher expression of caspase 1 (CASP1) and its activator NLRP3 in glucocorticoid resistant leukemia cells, due to significantly lower somatic methylation of CASP1 and NLRP3 promoters. Over-expression of CASP1 resulted in cleavage of the glucocorticoid receptor, diminished glucocorticoid-induced transcriptional response and increased glucocorticoid resistance. Knockdown or inhibition of CASP1 significantly increased glucocorticoid receptor levels and mitigated glucocorticoid resistance in CASP1 overexpressing ALL. Our findings establish a new mechanism by which the NLRP3/CASP1 inflammasome modulates cellular levels of the glucocorticoid receptor and diminishes cell sensitivity to glucocorticoids. The broad impact on glucocorticoid transcriptional response suggests this mechanism could also modify glucocorticoid effects in other diseases.
Publication Title
NALP3 inflammasome upregulation and CASP1 cleavage of the glucocorticoid receptor cause glucocorticoid resistance in leukemia cells.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 1 Downloadable Sample
- Affymetrix Human Genome U133A Array (hgu133a)
Description
Glucocorticoids are universally used in the treatment of acute lymphoblastic leukemia (ALL), and glucocorticoid resistance in leukemia cells confers a poor prognosis. To elucidate mechanisms of glucocorticoid resistance, we determined the prednisolone sensitivity of primary leukemia cells from 444 newly diagnosed ALL patients and found significantly higher expression of caspase 1 (CASP1) and its activator NLRP3 in glucocorticoid resistant leukemia cells, due to significantly lower somatic methylation of CASP1 and NLRP3 promoters. Over-expression of CASP1 resulted in cleavage of the glucocorticoid receptor, diminished glucocorticoid-induced transcriptional response and increased glucocorticoid resistance. Knockdown or inhibition of CASP1 significantly increased glucocorticoid receptor levels and mitigated glucocorticoid resistance in CASP1 overexpressing ALL. Our findings establish a new mechanism by which the NLRP3/CASP1 inflammasome modulates cellular levels of the glucocorticoid receptor and diminishes cell sensitivity to glucocorticoids. The broad impact on glucocorticoid transcriptional response suggests this mechanism could also modify glucocorticoid effects in other diseases.
Publication Title
NALP3 inflammasome upregulation and CASP1 cleavage of the glucocorticoid receptor cause glucocorticoid resistance in leukemia cells.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Expression 430A Array (moe430a)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Cyclical expression of the Notch/Wnt regulator Nrarp requires modulation by Dll3 in somitogenesis.
Sample Metadata Fields
Age, Specimen part
View Samples- Mus musculus
- 9 Downloadable Samples
- Affymetrix Mouse Expression 430A Array (moe430a)
Description
Mutations in the Notch1 receptor and delta-like 3 (Dll3) ligand cause global disruptions in axial segmental patterning. Genetic interactions between members of the notch pathway have previously been shown to cause patterning defects not observed in single gene disruptions. We examined Dll3-Notch1 compound mouse mutants to screen for potential gene interactions. While mice heterozygous at either locus appeared normal, 30% of Dll3-Notch1 double heterozygous animals exhibited localized, stochastic segmental anomalies similar to human congenital vertebral defects. Unexpectedly, double heterozygous mice also displayed statistically significant decreases in mandibular height and elongated maxillary hard palate. Examination of somite-stage embryos and perinatal anatomy and histology did not reveal any organ defects, so we used microarray-based analysis of Dll3 and Notch1 mutant embryos to identify gene targets that may be involved in notch-regulated segmental or craniofacial development. Therefore, Dll3-Notch1 double heterozygous mice model human congenital scoliosis and craniofacial disorders.
Publication Title
Dll3 and Notch1 genetic interactions model axial segmental and craniofacial malformations of human birth defects.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 4 Downloadable Samples
- Illumina HiSeq 2500
Description
Mutation or deletion of Neurofibromin (NF1), an inhibitor of RAS signaling, frequently occurs in epithelial ovarian cancer (EOC), supporting therapies that target downstream RAS effectors, such as the RAF-MEK-ERK pathway. However, no comprehensive studies have been carried out testing the efficacy of MEK inhibition in NF1-deficient EOC. Here, we performed a detailed characterization of MEK inhibition in NF1-deficient EOC cell lines using kinome profiling and RNA sequencing. Our studies showed MEK inhibitors were ineffective at providing durable growth inhibition in NF1-deficient cells due to kinome reprogramming. MEKi-mediated destabilization of FOSL1 resulted in induced expression of RTKs and their downstream RAF and PI3K signaling overcoming MEKi therapy. MEKi synthetic enhancement screens identified BRD2 and BRD4 as integral mediators of the MEKi-induced RTK signatures. Inhibition of BET proteins using BET bromodomain inhibitors (BETi) blocked MEKi-induced RTK reprogramming, indicating BRD2 and BRD4 represent promising therapeutic targets in combination with MEKi to block resistance due to kinome reprogramming in NF1-deficient EOC. Overall design: Examination of the global effects on transcription in response to trametinib (GSK212) in A1847 cells.
Publication Title
Intrinsic Resistance to MEK Inhibition through BET Protein-Mediated Kinome Reprogramming in NF1-Deficient Ovarian Cancer.
Sample Metadata Fields
Specimen part, Cell line, Treatment, Subject
View Samples- Arabidopsis thaliana
- 24 Downloadable Samples
- Affymetrix Arabidopsis Genome Array (ag)
Description
Gene expression profiles of a single Arabidopsis genotype (Col-0) in response to isogenic Pseudomonas syringae strains expressing one of four different cloned avr genes was studied (avrRpt2, avrRpm1, avrPphB, avrRps4; responses mediated by the R genes RPS2, RPM1, RPS5 and RPS4 ).
Publication Title
Discovery of ADP-ribosylation and other plant defense pathway elements through expression profiling of four different Arabidopsis-Pseudomonas R-avr interactions.
Sample Metadata Fields
Age, Specimen part, Disease, Disease stage
View Samples