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Homo sapiens
10 Downloadable Samples
NextSeq 500
Description
We sorted Eomes-negative NK cells (CD3- CD56+ CXCR6- CD16-) and Eomes-positive NK cells (CD3- CD56+ CXCR6+) from total leukocytes isolated from the perfusion fluid of five healthy human livers destined for transplantation. Total RNA was extracted from sorted cells, cDNA generated and RNASeq performed. Overall design: Examination of mRNA levels in paired Eomes-negative/Eomes-positive NK cells from the same donor.
Publication Title
Eomeshi NK Cells in Human Liver Are Long-Lived and Do Not Recirculate but Can Be Replenished from the Circulation.
Sample Metadata Fields
Specimen part, Subject
View Samples- Mus musculus
- 14 Downloadable Samples
Affymetrix Mouse Expression 430A Array (moe430a)
Description
Genes encoding transcription factors function as hubs in gene regulatory networks because they encode DNA-binding proteins, which bind to promoters that carry their binding sites. In the present work we have studied gene regulatory networks defined by genes with transcripts belonging to different mRNA abundance classes in the small intestinal epithelial cell. The focus is the rewiring that occurs in transcription factor hubs in these networks during the differentiation of the small intestinal epithelial cell while it migrates along the crypt-villus axis and during its development from a fetal endodermal cell to a mature adult villus epithelial cell.
Publication Title
Metabolome, transcriptome, and bioinformatic cis-element analyses point to HNF-4 as a central regulator of gene expression during enterocyte differentiation.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 60 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a), Affymetrix Human Full Length HuGeneFL Array (hu6800)
Description
We developed a general approach to small molecule library screening called GE-HTS (Gene Expression-Based High Throughput Screening) in which a gene expression signature is used as a surrogate for cellular states and applied it to the identification of compounds inducing the differentiation of acute myeloid leukemia cells. In screening 1,739 compounds, we identified 8 that reliably induced the differentiation signature, and furthermore yielded functional evidence of bona fide differentiation.
Publication Title
Gene expression-based high-throughput screening(GE-HTS) and application to leukemia differentiation.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 50 Downloadable Samples
Affymetrix Human Genome U133A Array (hgu133a), Affymetrix Human Full Length HuGeneFL Array (hu6800)
Description
We developed a general approach to small molecule library screening called GE-HTS (Gene Expression-Based High Throughput Screening) in which a gene expression signature is used as a surrogate for cellular states and applied it to the identification of compounds inducing the differentiation of acute myeloid leukemia cells. In screening 1,739 compounds, we prioritized 15 candidate compounds (2 were already confirmed in the literature). We next evaluated the 13 remaining compounds. Eight reliably induced the differentiation signature, and furthermore yielded functional evidence of bona fide differentiation.
Publication Title
Gene expression-based high-throughput screening(GE-HTS) and application to leukemia differentiation.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 69 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
Cure rates for patients with acute myeloid leukemia (AML) remain low despite ever-increasing dose intensity of cytotoxic therapy. In an effort to identify novel approaches to AML therapy, we recently reported a new method of chemical screening based on the modulation of a gene expression signature of interest. We applied this approach to the discovery of AML-differentiation-promoting compounds. Among the compounds inducing neutrophilic differentiation was DAPH1 (4,5-dianilinophthalimide), previously reported to inhibit epidermal growth factor receptor (EGFR) kinase activity. Here we report that the Food and Drug Administration (FDA)-approved EGFR inhibitor gefitinib similarly promotes the differentiation of AML cell lines and primary patient-derived AML blasts in vitro. Gefitinib induced differentiation based on morphologic assessment, nitro-blue tetrazolium reduction, cell-surface markers, genome-wide patterns of gene expression, and inhibition of proliferation at clinically achievable doses. Importantly, EGFR expression was not detected in AML cells, indicating that gefitinib functions through a previously unrecognized EGFR-independent mechanism. These studies indicate that clinical trials testing the efficacy of gefitinib in patients with AML are warranted.
Publication Title
Gefitinib induces myeloid differentiation of acute myeloid leukemia.
Sample Metadata Fields
Disease, Disease stage, Cell line
View Samples- Homo sapiens
- 21 Downloadable Samples
- Affymetrix Human Full Length HuGeneFL Array (hu6800), Affymetrix Human Genome U133A Array (hgu133a)
Description
We developed a general approach to small molecule library screening called GE-HTS (Gene Expression-Based High Throughput Screening) in which a gene expression signature is used as a surrogate for cellular states and applied it to the identification of compounds inducing the differentiation of acute myeloid leukemia cells. In screening 1,739 compounds, we identified 8 that reliably induced the differentiation signature, and furthermore yielded functional evidence of bona fide differentiation. We tested several of these in duplicate replicates in blasts from a patient with APL. Also included in this data set are a collection of 6 primary patient AML cells, 3 normal neutrophils samples, and 3 normal monocyte samples. This data was used to evaluate whole genome effects of the compounds on APL cells in relation to AML versus normal neutrophils and monocytes.
Publication Title
Gene expression-based high-throughput screening(GE-HTS) and application to leukemia differentiation.
Sample Metadata Fields
No sample metadata fields
View Samples
GSE5007- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
This study compared the expression signatures of HL60 cells +/- tretinoin. This data was then used for another study showing a method for high-throughput gene expression signature analysis.
Publication Title
A method for high-throughput gene expression signature analysis.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 4 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
NK cells are believed to contribute to the control of hepatitis C virus infection and pathogenesis of liver disease. Standard treatment of both acute and chronic hepatitis C is based on the administration of interferon alpha, however, the effects of type I interferons on human NK cells have not been studied in the context of hepatitis C. We therefore first performed a microarray screen for genes differentially regulated in human NK cells after stimulation of PBMC with recombinant interferon alpha-2b. One of the genes upregulated was TRAIL which was confirmed in vitro on the protein level.
Publication Title
Interferon-alpha-induced TRAIL on natural killer cells is associated with control of hepatitis C virus infection.
Sample Metadata Fields
Sex, Specimen part, Treatment
View Samples GSE15648- Homo sapiens
- 30 Downloadable Samples
- Affymetrix Human Genome U95A Array (hgu95a)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Identification of AML1-ETO modulators by chemical genomics.
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 30 Downloadable Samples
- Affymetrix Human Genome U95A Array (hgu95a)
Description
Somatic rearrangements of transcription factors are common abnormalities in the acute leukemias. With rare exception, however, the resultant protein products have remained largely intractable as pharmacologic targets. One example is AML1-ETO, the most common translocation reported in acute myeloid leukemia (AML). To identify AML1-ETO modulators, we screened a small molecule library using a chemical genomic approach. Gene expression signatures were used as surrogates for the expression versus loss of the translocation in AML1-ETO-expressing cells. The top classes of compounds that scored in this screen were corticosteroids and dihydrofolate reductase (DHFR) inhibitors. In addition to modulating the AML1-ETO signature, both classes induced evidence of differentiation, dramatically inhibited cell viability, and ultimately induced apoptosis via on-target activity. Furthermore, AML1-ETO-expressing cell lines were exquisitely sensitive to the effects of corticosteroids on cellular viability compared with nonexpressers. The corticosteroids diminished AML1-ETO protein in AML cells in a proteasome- and glucocorticoid receptor-dependent manner. Moreover, these molecule classes demonstrated synergy in combination with standard AML chemotherapy agents and activity in an orthotopic model of AML1-ETO-positive AML. This work suggests a role for DHFR inhibitors and corticosteroids in treating patients with AML1-ETO-positive disease.
Publication Title
Identification of AML1-ETO modulators by chemical genomics.
Sample Metadata Fields
Disease, Disease stage, Cell line
View Samples