In the developing embryo, haematopoietic stem cells (HSCs) emerge from the aorta-gonad-mesonephros (AGM) region but the molecular regulation of this process is poorly understood. Recently, the progression from E9.5 to E10.5 and polarity along the dorso-ventral axis have been identified as clear demarcations of the supportive HSC niche. To identify novel secreted regulators of HSC maturation, we performed RNA-sequencing over these spatio-temporal transitions in the AGM region, and supportive OP9 cell line. Overall design: RNA-sequencing profiles of the aorta-gonad-mesonephros region from E9.5 embryos and E10.5 embryos sub-dissected into dorsal (AoD), ventral (AoV) and urogenital ridges (UGR) and pooled from between 15 and 34 embryos in three separate experiments.
A molecular roadmap of the AGM region reveals BMPER as a novel regulator of HSC maturation.
Specimen part, Subject
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Identification of the genes regulated by Wnt-4, a critical signal for commitment of the ovary.
Sex, Specimen part
View SamplesIn the developing embryo, haematopoietic stem cells (HSCs) emerge from the aorta-gonad-mesonephros (AGM) region but the molecular regulation of this process is poorly understood. Recently, the progression from E9.5 to E10.5 and polarity along the dorso-ventral axis have been identified as clear demarcations of the supportive HSC niche. To identify novel secreted regulators of HSC maturation, we performed RNA-sequencing over these spatio-temporal transitions in the AGM region, and supportive OP9 cell line. Overall design: RNA-sequencing profiles of OP9 cells grown in flat, submersed culture or reaggregate and cultured at the liquid-gas interface were compared.
A molecular roadmap of the AGM region reveals BMPER as a novel regulator of HSC maturation.
Specimen part, Cell line, Subject
View SamplesWnt-4 signaling is critical for embryonic female sexual development. When Wnt-4 gene is deleted during embryonic development, the knock-out females present a partial sex reversal.
Identification of the genes regulated by Wnt-4, a critical signal for commitment of the ovary.
Specimen part
View SamplesWnt-4 signaling is critical for embryonic female sexual development. When Wnt-4 gene is deleted during embryonic development, the knock-out females present a partial sex reversal.
Identification of the genes regulated by Wnt-4, a critical signal for commitment of the ovary.
Sex, Specimen part
View SamplesBACKGROUND: Cadmium is implicated in prostate carcinogenesis, but its oncogenic action remains unclear.
Transcriptome analyses in normal prostate epithelial cells exposed to low-dose cadmium: oncogenic and immunomodulations involving the action of tumor necrosis factor.
Sex
View SamplesCarbon nanotubes (CNTs) are fibrous particulates made up of elemental carbon and a novel nanomaterial known for its variety of industrial applications. It has been shown that lung exposure to CNTs may cause adverse effects inclunding lung inflammation and remodeling in experimental models. We investigated the impact of genetic background on the development of adverse outcomes by comparing several common inbred mouse strains and found that C57Bl/6 and DBA/2 strains were polarized in their sensitivity to adverse changes at 4 weeks following an exposure to 4 mg/kg CNT. Here we compare underlying gene expression profiles which may inform the understanding of lung biology underpinning genetic susceptibility to adverse outcomes following environmental or occupational exposure to CNTs. Overall design: Changes in mRNA profiles were compared between CNT-exposed animals and vehicle-treated controls (n=3/group) of either C57Bl/6 or DBA/2 strains.
Genetic susceptibility to toxicologic lung responses among inbred mouse strains following exposure to carbon nanotubes and profiling of underlying gene networks.
Specimen part, Subject
View SamplesThe ability of chromatin to switch back and forth from open euchromatin to closed heterochromatin is vital for transcriptional regulation and genomic stability, and subject to disruption by exposure to environmental agents such as hexavalent chromium. Cr(VI) exposure can cause chromosomal disruption through formation of Cr-DNA adducts, free radical-induced DNA damage, and DNA-Cr-protein and DNA-Cr-DNA cross-links, all of which may disrupt chromatin remodeling mechanisms responsible for maintenance or controlled modification of epigenetic homeostasis. In addition, dose-response analyses have shown that acute exposures to high-concentrations of Cr(VI) and chronic exposures to low-concentrations of the same agent lead to significantly different transcriptomic and genomic stability outcomes. To investigate how transcriptional responses to chromium exposure might correlate to structural changes in chromatin, we have used whole genome Formaldehyde-Assisted Isolation of Regulatory Elements (FAIRE) analysis coupled with deep sequencing to identify regions of the genome that switch from open to closed chromatin or vice versa in response to exposure to varying Cr(VI) concentrations. We find that the switch affects gene expression levels in the target areas that vary depending on Cr(VI) concentration. At either Cr(VI) concentration, chromatin domains surrounding binding sites for AP-1 transcription factors become significantly open, treatment whereas BACH2 and CTCF binding sites are open solely at the low and high concentrations, respectively. Our results suggest that FAIRE may be a useful technique to map chromatin elements targeted by DNA damaging agents for which there is no prior knowledge of their specificity, and to identify subsequent transcriptomic changes induced by those agents. Overall design: Cr25 treatment and control samples are in duplicate for RNA-seq, and no replicate for FAIRE-seq. Cr0.5 treatment and control samples are in duplicate for RNA-seq, and no replicate for FAIRE-seq.
Formaldehyde-Assisted Isolation of Regulatory Elements (FAIRE) analysis uncovers broad changes in chromatin structure resulting from hexavalent chromium exposure.
No sample metadata fields
View SamplesTranscriptome analysis of MCF-7 cells exposed for 48 hours to various concentrations of xenoestrogen chemicals.
Expressomal approach for comprehensive analysis and visualization of ligand sensitivities of xenoestrogen responsive genes.
Cell line
View SamplesThe aryl hydrocarbon receptor (AHR) is a ligand activated transcription factor that regulates the expression of xenobiotic detoxification genes and is a critical mediator of gene-environment interactions. In addition, many AHR target genes that have been identified by genome-wide profiling have morphogenetic functions, suggesting that AHR activation may play a role in embryonic development. To address this hypothesis, we studied the consequences of AHR activation by TCDD, its prototypical ligand, during spontaneous mouse ES cell differentiation into contractile cardiomyocytes. Treatment with TCDD or shRNA-mediated AHR knockdown significantly decreased the ability of cardiomyocytes to contract and the expression of cardiac markers in these cells. An AHR-positive embryonic stem cell lineage was generated that expressed puromycin resistance and eGFP under the control of the AHR-responsive Cyp1a1 promoter. Cells of this lineage were over 90% pure and expressed AHR as well as cardiomyocyte markers. Analysis of temporal trajectories of global gene expression in these cells shows that activation of the AHR/TCDD axis disrupts the concerted expression of genes that regulate multiple signaling pathways involved in cardiac and neural morphogenesis and differentiation, including dozens of genes encoding homeobox transcription factors and Polycomb and Trithorax Group genes. More than 50% of the homeobox factors so regulated do not have AhRE sites in their promoters, indicating that AHR activation may establish a complex regulatory network that reaches beyond direct AHR signaling and is capable of disrupting various aspects of embryonic development, including cardiomyocyte differentiation. Overall design: mRNA profiles of WT and selected AHR positive cells at different differentiation days treated with and without TCDD in duplicates
Disruption of aryl hydrocarbon receptor homeostatic levels during embryonic stem cell differentiation alters expression of homeobox transcription factors that control cardiomyogenesis.
Treatment, Subject
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