The human and mouse aryl hydrocarbon receptor (hAHR and mAHRb) share limited (58%) transactivation domain sequence identity. Compared to the mAHRb allele, the hAHR displays 10-fold lower relative affinity for prototypical ligands such as 2,3,7,8 tetrachlorodibenzo-p-dioxin (TCDD). However, in previous studies we have demonstrated that the hAHR can display a higher relative ligand binding affinity than the mAHRb for specific AHR ligands such as indirubin. Each receptor has also been shown to differentially recruit LXXLL co-activator-motif proteins and to utilize different TAD subdomains in gene transactivation. Using hepatocytes isolated from C57BL6/J mice (Ahrb/b) and AHRTtr transgenic mice which express hAHR protein specifically in hepatocytes, we investigated whether the hAHR and mAHRb differentially regulate genes. Microarray and quantitative-PCR analysis of Ahrb/b and AHRTtr primary-mouse hepatocytes treated with 10 nM TCDD revealed that a number of established AHR target genes such as Cyp1a1 and Cyp1b1 are significantly induced by both receptors. Remarkably, of the 1752 genes induced by mAHRb and 1186 genes induced by hAHR, only 265 genes (<10%) were significantly activated by both receptors in response to TCDD. Conversely of the 1100 and 779 genes significantly repressed in mAHRb and hAHR hepatocytes respectively, only 462 (<25%) genes were significantly repressed by both receptors in response to TCDD treatment. Genes identified as differentially expressed are known to be involved in a number of biological pathways, including cell proliferation and inflammatory response which suggests that compared to the mAHRb, the hAHR may play contrasting roles in TCDD-induced toxicity and endogenous AHR-mediated gene regulation.
Differential gene regulation by the human and mouse aryl hydrocarbon receptor.
Specimen part
View SamplesAlthough practiced clinically for more than 40 years, the use of hematopoietic stem cell (HSC) transplants remains limited by the ability to expand these cells ex vivo. An unbiased screen with primary human HSCs identified a purine derivative, StemRegenin 1 (SR1), that promotes the ex vivo expansion of CD34+ cells. Culture of HSCs with SR1 led to a 50-fold increase in cells expressing CD34 and a 17-fold increase in cells that retain the ability to engraft immunodeficient mice. Mechanistic studies show that SR1 acts by antagonizing the aryl hydrocarbon receptor (AHR). The identification of SR1 and AHR modulation as a means to induce ex vivo HSC expansion should facilitate the clinical use of HSC therapy.
Aryl hydrocarbon receptor antagonists promote the expansion of human hematopoietic stem cells.
Specimen part, Time
View SamplesCD4+ and CD8+ T cells isolated from wild-type and Foxo1-deficient mice were analyzed by global gene expression profiling with Affymetrix array MOE 430 2.0. Results indicate Foxo1 regulates the expression of genes encoding positive regulators of T cell activation, differentiation, homeostasis, cell adhesion, cell migration, and cellular stress responses.
An essential role of the Forkhead-box transcription factor Foxo1 in control of T cell homeostasis and tolerance.
Specimen part
View SamplesWe found that Hopx is required for the function of DC-induced regulatory T cells in vivo. We used microarrays to identify relevant Hopx-targets in such cells after antigenic re-challenge in vivo.
The transcription cofactor Hopx is required for regulatory T cell function in dendritic cell-mediated peripheral T cell unresponsiveness.
Specimen part
View SamplesPurpose: To compare the transcriptomes of IL-21-expressing, IL-21 and IL-4-expressing, and IL-4 expressing follicular helper T (Tfh) cells and Th2 cells in the spleen at 8 days following helminth infection Methods: Cell sorting of the populations was done for CD4+B220-CD44hiCXCR5hiPD-1hi cells of the various types, followed by mRNA purification. Overall design: CD4+Splenic T cell mRNA profiles 8 days post-infection of IL-21/IL-4 dual reporter mice with Nippostrongylus brasiliensis were generated by mRNA sequencing using Illumina HiSeq 2000.
TFH cells progressively differentiate to regulate the germinal center response.
Specimen part, Subject
View SamplesMicroarray analysis of Myd88-/-Trif-/- and Myd88-/-Rip2-/- macrophage responses to WT or dotA mutant L. pneumophila.
Type IV secretion-dependent activation of host MAP kinases induces an increased proinflammatory cytokine response to Legionella pneumophila.
No sample metadata fields
View SamplesExpression profiling in hippocampal neurons to identify activity-regulated genes controlled by MEF2
Genome-wide analysis of MEF2 transcriptional program reveals synaptic target genes and neuronal activity-dependent polyadenylation site selection.
No sample metadata fields
View SamplesExpression profiling in hippocampal neurons to identify genes upregulated in response to ectopic MEF2 activation by MEF2-VP16-ER
Genome-wide analysis of MEF2 transcriptional program reveals synaptic target genes and neuronal activity-dependent polyadenylation site selection.
No sample metadata fields
View SamplesExpression profiling in whole rat forebrain in response to exposure of animals to a novel environment
Genome-wide analysis of MEF2 transcriptional program reveals synaptic target genes and neuronal activity-dependent polyadenylation site selection.
No sample metadata fields
View SamplesIn this study, we examined differential gene expression in nave human CD4+ T cells, as well as in effector Th1, Th17-negative and Th17-enriched CD4- T cell subsets. We observed a marked enrichment for increased gene expression in effector CD4+ T cells compared to naive CD4+ among immune-mediated disease oci genes. Within effector T cells, expression of disease-associated genes was increased in Th17-enriched compared to Th17-negative cells.
Effector CD4+ T cell expression signatures and immune-mediated disease associated genes.
Specimen part
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