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Homo sapiens
144 Downloadable Samples
Illumina humanRef-8 v2.0 expression beadchip
Description
Human toxicogenomic studies to date have been of limited size, have mainly addressed exposures at the upper end of typical ranges of human exposure, and have often lacked precise, individual estimates of exposure. Previously, we identified genes associated with exposure to high (>10 ppm) levels of the leukemogen, benzene, through transcriptomic analyses of blood cells from small numbers of occupationally exposed workers. Here, we have expanded the study to 125 workers exposed to a wide range of benzene levels, including <1 ppm. Study design, and analysis with a mixed effects model, removed sources of biological and experimental variability and revealed highly significant widespread perturbation of gene expression at all exposure levels. Benzene is an established cause of acute myeloid leukemia (AML), and may cause one or more lymphoid malignancies in humans. Interestingly, acute myeloid leukemia was among the most significant pathways impacted by benzene exposure in the present study. Further, at most exposure levels, immune response pathways including T cell receptor signaling, B cell receptor signaling, and Toll like receptor signaling were impacted, providing support for the biological plausibility of an association between lymphoma and benzene exposure. We also identified a 16-gene expression signature modified by all levels of benzene exposure, comprising genes with roles in immune response, inflammatory response, cell adhesion, cell-matrix adhesion, and blood coagulation. Overall, these findings support, and expand upon, our current understanding of the mechanisms by which benzene may induce hematotoxicity, leukemia and lymphoma. Furthermore, this study shows that with good study design and analysis, transcriptome profiling of the blood of chemically-exposed humans can identify relevant biomarkers across a range of exposures and inform about potential associations with disease risks.
Publication Title
Global gene expression profiling of a population exposed to a range of benzene levels.
Sample Metadata Fields
Sex, Age, Subject
View Samples- Mus musculus
- 86 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Dynamic regulatory network controlling TH17 cell differentiation.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Drosophila melanogaster
- 64 Downloadable Samples
- Affymetrix Drosophila Genome 2.0 Array (drosophila2)
Description
Translational control is critical for early Drosophila embryogenesis and is exerted mainly at the gene-specific level.
Publication Title
Global analyses of mRNA translational control during early Drosophila embryogenesis.
Sample Metadata Fields
No sample metadata fields
View Samples- Anopheles gambiae
- 62 Downloadable Samples
- Affymetrix Plasmodium/Anopheles Genome Array (plasmodiumanopheles)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Developmental and evolutionary basis for drought tolerance of the Anopheles gambiae embryo.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 58 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Despite their enormous importance, the molecular circuits that control the differentiation of Th17 cells remain largely unknown. Recent studies have reconstructed regulatory networks in mammalian cells, but have focused on short-term responses and relied on perturbation approaches that cannot be applied to primary T cells. Here, we develop a systematic strategy combining transcriptional profiling at high temporal resolution, novel computational algorithms, and innovative nanowire-based tools for performing gene perturbations in primary T cells to derive and experimentally validate a temporal model of the dynamic regulatory network that controls Th17 differentiation. The network is arranged into two self-reinforcing and mutually antagonistic modules that either suppress or promote Th17 differentiation. The two modules contain 12 novel regulators with no previous implication in Th17 differentiation, which may be essential to maintain the appropriate balance of Th17 and other CD4+ T cell subsets. Overall, our study identifies and validates 39 regulatory factors that are embedded within a comprehensive temporal network and identifies novel drug targets and organizational principles for the differentiation of Th17 cells.
Publication Title
Dynamic regulatory network controlling TH17 cell differentiation.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Anopheles gambiae
- 56 Downloadable Samples
- Affymetrix Plasmodium/Anopheles Genome Array (plasmodiumanopheles)
Description
In order to examine the gene expression in the course of mosquito embryogenesis, microarray assays were performed on staged A. gambiae embryos, from fertilization to 52 hours of development (which is close to hatching at ~50 hours post-fertilization). RNA was extracted from staged embryos roughly every three hours after fertilization, and then hybridized to the A. gambiae transcriptome microarray.
Publication Title
Developmental and evolutionary basis for drought tolerance of the Anopheles gambiae embryo.
Sample Metadata Fields
No sample metadata fields
View Samples
GSE9088- Drosophila melanogaster
- 29 Downloadable Samples
- Affymetrix Drosophila Genome Array (drosgenome1)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Genomic profiling and expression studies reveal both positive and negative activities for the Drosophila Myb MuvB/dREAM complex in proliferating cells.
Sample Metadata Fields
Treatment
View Samples- Drosophila melanogaster
- 29 Downloadable Samples
- Affymetrix Drosophila Genome Array (drosgenome1)
Description
Myb-MuvB (MMB)/dREAM is a nine subunit complex first described in Drosophila as a repressor of transcription, dependent upon E2F2 and the RBFs. Myb, an integral member of MMB, curiously plays no role in the silencing of the test genes previously analyzed. Moreover, Myb plays an activating role in DNA replication in Drosophila egg chamber follicle cells. The essential functions for Myb are executed as part of MMB. This duality of function lead to the hypothesis that MMB, which contains both known activator and repressor proteins, might function as part of a switching mechanism that is dependent upon DNA sites and developmental context.
Publication Title
Genomic profiling and expression studies reveal both positive and negative activities for the Drosophila Myb MuvB/dREAM complex in proliferating cells.
Sample Metadata Fields
Treatment
View Samples- Mus musculus
- 20 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Despite their enormous importance, the molecular circuits that control the differentiation of Th17 cells remain largely unknown. Recent studies have reconstructed regulatory networks in mammalian cells, but have focused on short-term responses and relied on perturbation approaches that cannot be applied to primary T cells. Here, we develop a systematic strategy combining transcriptional profiling at high temporal resolution, novel computational algorithms, and innovative nanowire-based tools for performing gene perturbations in primary T cells to derive and experimentally validate a temporal model of the dynamic regulatory network that controls Th17 differentiation. The network is arranged into two self-reinforcing and mutually antagonistic modules that either suppress or promote Th17 differentiation. The two modules contain 12 novel regulators with no previous implication in Th17 differentiation, which may be essential to maintain the appropriate balance of Th17 and other CD4+ T cell subsets. Overall, our study identifies and validates 39 regulatory factors that are embedded within a comprehensive temporal network and identifies novel drug targets and organizational principles for the differentiation of Th17 cells.
Publication Title
Dynamic regulatory network controlling TH17 cell differentiation.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Rattus norvegicus
- 19 Downloadable Samples
- Affymetrix Rat Genome 230 2.0 Array (rat2302)
Description
Insults to the cerebral cortex, such as trauma, ischemia or infections, may result in the development of epilepsy, one of the most common neurological disorders. Previous studies have suggested that perturbations in neurovascular integrity and breakdown of the blood-brain barrier (BBB) lead to neuronal hypersynchronization and epileptiform activity, but the underlying mechanisms are unknown. As with BBB opening, treatment with albumin or with TGF-1 results in the development of hypersynchronized epileptiform activity. Given the latent period before the appearance of epileptiform activity, we hypothesized the underlying mechanism is a transcriptional response which would be similar for BBB breakdown and exposure to albumin or TGF-1. In search of a common pathway and transcriptional activation pattern we performed a genome wide analysis. Genomic expression analyses demonstrated similar expression patterns for BBB opening, albumin and TGF-1 exposure. Most importantly, TGF- pathway blockers suppressed most albumin-induced transcriptional changes.
Publication Title
Astrocytic dysfunction in epileptogenesis: consequence of altered potassium and glutamate homeostasis?
Sample Metadata Fields
Sex
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