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GSE72276
Rattus norvegicus
81 Downloadable Samples
Affymetrix Rat Gene 2.0 ST Array (ragene20st)
Description
Exposure to common environmental chemicals, including those found in personal care products has been linked to mammary cancer at high doses in animal models. Their effects at low doses at levels comparable to human exposure, especially during critical windows of development remain poorly understood. Using a Sprague-Dawley rat model, we investigated the effects of of three environmental chemicals diethyl phthalate (DEP), methyl paraben (MPB) and triclosan (TCS) on the transcriptome of normal developing mammary glands at low doses mimicking human exposure. Rats were exposed during three windows of early development perinatal (gestation day (GD) 1 - 20 or postnatal day (PND) 1 - 20), prepubertal (PND 21 - 41) and pubertal (PND 42 - 62), as well as chronic exposure from birth to end of lactation (PND 1 - 146). Mammary gland whole-transcriptomes were profiled by Affymetrix rat gene 2.0 st arrays.
Publication Title
Changes in mammary histology and transcriptome profiles by low-dose exposure to environmental phenols at critical windows of development.
Sample Metadata Fields
Sex, Specimen part
View Samples- Rattus norvegicus
- 31 Downloadable Samples
- Affymetrix Rat Gene 2.0 ST Array (ragene20st)
Description
There is a lack of systematic investigations of large-scale transcriptome patterns associated with normal breast development. Herein, we profiled whole-transcriptome (by microarrays) of normal mammary glands in female Sprague-Dawley rats, an animal model widely used in breast cancer research, across six distinctive developmental stages pre-pubertal, peri-pubertal, pubertal, lactation, and adult parous and age-matched nulliparous.
Publication Title
Histology and Transcriptome Profiles of the Mammary Gland across Critical Windows of Development in Sprague Dawley Rats.
Sample Metadata Fields
Sex, Specimen part
View Samples- Homo sapiens
- 36 Downloadable Samples
- Illumina HumanHT-12 V3.0 expression beadchip
Description
Therapeutic targeting of BRAFV600Eand of MEK has shown a significant impact on progression-free and overall survival in advanced melanoma, but only a fraction of patients benefit from these treatments, suggesting that additional signaling pathways involved in melanoma growth/survival need to be identified. To this end, we used whole genome microarray analysis to identify differentially expressed genes in a set of neoplastic clones, isolated from a single melanoma metastasis, and characterized by mututally exclusive expression of BRAFV600E or NRASQ61R. By this approach we identified two genes, SEMA6A and Mical-1 belonging to the semaphorin-plexin signaling pathway and higly expressed, at mRNA and protein level, in BRAF-mutant neoplastic clones. Real-time PCR, Western blot analysis and immunohistochemistry confirmed the preferential expression of SEMA-6A and Mical-1 in BRAFV600E neoplastic cells from melanoma clones, primary and metastatic cell lines and tissue sections from melanoma lesions. SEMA6A depletion, by specific RNA-interference experiments, led to cytoskeletal remodeling, loss of stress fibers, generation of actin-rich protrusion, and cell death, whereas SEMA6A overexpression, in NRASQ61R clones, promoted invasiveness. Mical-1 depletion, by siRNA, in BRAFV600E melanomas, did not alter the actin cytoskeleton organization but caused a strong NDR phosphorylation and NDR-dependent apoptosis. Overall, these results suggest that the SEMA and MICAL pathways contribute to promote survival of BRAFV600E melanomas.
Publication Title
Sema6A and Mical1 control cell growth and survival of BRAFV600E human melanoma cells.
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 3 Downloadable Samples
Description
Pheochromocytomas/paragangliomas are the most heritable of all tumors. However, there are still cases that are not explained by mutations in the known genes. We aimed to identify the genetic cause of disease in a patient strongly suspected of having hereditary tumors. We identified a novel de novo mutation in DNMT3A, affecting a highly conserved residue. Among other results from other techniques, a different global expression profile was observed in the patient carrying the mutated DNMT3A compared to controls (parents) by RNA-seq
Publication Title
Gain-of-function mutations in DNMT3A in patients with paraganglioma.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 8 Downloadable Samples
- Illumina Genome Analyzer
Description
In germ cells, Piwi proteins interact with a specific class of small non-coding RNAs, piwi-interacting RNAs (piRNAs). Together, these form a pathway that represses transposable elements, thus safeguarding germ cell genomes. While basic models describe the operation of piRNA pathways, neither the protein compositions of Piwi complexes, the critical protein-protein interactions that drive small RNA production and target recognition, or the precise molecular consequences of conserved localization to germline structures, call nuage, is well understood. We purified the three murine Piwi family proteins, Mili, Miwi, and Miwi2, from mouse germ cells and characterized their interacting protein partners. Piwi proteins were found in complex with Prmt5/Wdr77, an enzyme that di-methylates arginine residues. By immunoprecipitation with specific antibodies and by mass spectrometry, we found that Piwi proteins are arginine methylated at conserved positions in their amino termini. These modifications are essential to direct complex formation with specific Tudor-domain proteins, whose interactions with Piwis can be required for localization of RNP complexes in cytoplasmic nuage, proper piRNA expression, and transposon silencing. Considered together, our findings indicate that arginine methylation drives the assembly of multi-protein machines whose integrity and specific sub-cellular localization is necessary for efficient function of the piRNA pathway. Keywords: gene regulation study Overall design: Total small RNA in embryonic and post-birth mouse testes of tdrd1 and tdrd6 mutants
Publication Title
RNF17 blocks promiscuous activity of PIWI proteins in mouse testes.
Sample Metadata Fields
No sample metadata fields
View Samples- Gallus gallus
- 6 Downloadable Samples
- Affymetrix Chicken Genome Array (chicken)
Description
Modern functional genomic approaches may help to better understand the molecular events involved in tissue morphogenesis and to identify molecular signatures and pathways. We have recently applied transcriptomic profiling to evidence molecular signatures in the development of the normal chicken chorioallantoic membrane and in tumor engrafted on the CAM. We have now extended our studies by performing a transcriptome analysis in the wound model of the chicken CAM which is another relevant model of tissue morphogenesis. To induce granulation tissue formation, we performed wounding of the chicken CAM and compared gene expression to normal CAM at the same stage of development. Matched control samples from the same individual were used. We observed a total of 282 genes up-regulated and 44 genes downregulated assuming a false-discovery rate at 5 % and a fold change > 2. Furthermore, bioinformatics analysis lead to the identification of several categories that are associated to organismal injury, tissue morphology, cellular movement, inflammatory disease, development and immune system. Endothelial cell data filtering leads to the identification of several new genes with an endothelial cell signature. In summary, the chick chorioallantoic wound model allows the identification of gene signatures involved in granulation tissue formation and neoangiogenesis. This may constitute a fertile ground for further studies.
Publication Title
Gene signatures in wound tissue as evidenced by molecular profiling in the chick embryo model.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 17 Downloadable Samples
- Illumina HiSeq 1000
Description
Mammalian spermatogonial stem cells (SSCs) spontaneously convert to multipotent adult spermatogonial-derived stem cells (MASCs) during in vitro expansion. Here, we examine the epigenetic signature of SSCs and MASCs, identifying bivalent histone H3-lysine4 and -lysine27 trimethylation at somatic gene promoters in SSCs and an ESC-like promoter chromatin state in MASCs. Overall design: Examination of gene expression in different cell types.
Publication Title
Epigenetic profiles signify cell fate plasticity in unipotent spermatogonial stem and progenitor cells.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Zea mays
- 8 Downloadable Samples
- Illumina Genome Analyzer II
Description
P1 encodes an R2R3-MYB transcription factor responsible for the accumulation of insecticidal flavones in maize silks and red phlobaphene pigments in pericarps and other floral tissues, which contributed to making P1 an important visual marker since the dawn of modern genetics. We conducted RNA-Seq using pericarps at two different stages, 14 and 25 days after pollination (DAP). High-throughput sequencing using the Illumina platform resulted in the generation of ~20 million high quality reads, from which ~90% aligned to the recently completed maize genome sequence corresponding to ~5 million reads for each one of the four samples. Overall design: Examination of two different RNA samples from two different stages of maize pericarp tissues.
Publication Title
A genome-wide regulatory framework identifies maize pericarp color1 controlled genes.
Sample Metadata Fields
Specimen part, Subject
View Samples- Zea mays
- 2 Downloadable Samples
- Illumina Genome Analyzer II
Description
P1 encodes an R2R3-MYB transcription factor responsible for the accumulation of insecticidal flavones in maize silks and red phlobaphene pigments in pericarps and other floral tissues, which contributed to making P1 an important visual marker since the dawn of modern genetics. We conducted RNA-Seq using from maize silks obtained at 2-3 days after emergence. High-throughput sequencing using the Illumina platform resulted in the generation of ~14 million high quality reads, corresponding to ~7 million reads for each sample, from which 76% aligned to the maize genome. Overall design: Examination of two different RNA samples from maize silks obtained at 2-3 days after emergence
Publication Title
A genome-wide regulatory framework identifies maize pericarp color1 controlled genes.
Sample Metadata Fields
Specimen part, Subject
View Samples- Danio rerio
- 4 Downloadable Samples
- IlluminaHiSeq2000
Description
Exposure to bisphenol A (BPA), an endocrine disruptor (ED), has raised concerns for both human and ecosystem health. Epigenetic factors, including microRNAs, are key regulators of gene expression during cancer. The effect of BPA exposure on the zebrafish epigenome remains poorly characterized. Zebrafish represents an excellent model to study cancer as the organism develops disease that resembles human cancer. Using zebrafish as systems toxicology model, we hypothesized that chronic BPA-exposure impacts the miRNome in adult zebrafish and establishes an epigenome more susceptible to cancer development. After a 21 day exposure to 100 nM BPA, RNA from the liver was extracted to perform high throughput mRNA and miRNA sequencing. Differential expression (DE) analyses comparing BPA-exposed to control specimens were performed using established bioinformatics pipelines. In the BPA-exposed liver, 6,188 mRNAs and 15 miRNAs were differently expressed (q = 0.1). By analyzing human orthologs of the DE zebrafish genes signatures associated with non-alcoholic fatty liver disease (NAFLD), oxidative phosphorylation, mitochondrial dysfunction and cell cycle were uncovered. Chronic exposure to BPA has a significant impact on the liver miRNome in adult zebrafish and has the potential to cause adverse outcomes including cancer. Overall design: Examination of transcriptome changes in an in vivo model organism exposed to a common, environmental compound.
Publication Title
The Plasticizer Bisphenol A Perturbs the Hepatic Epigenome: A Systems Level Analysis of the miRNome.
Sample Metadata Fields
No sample metadata fields
View Samples