ZXDC1 augments the expression of various markers of monocyte/macrophage differentiation when over-expressed in the U937 cell line treated with the phorbol ester PMA. Likewise, knockdown of ZXDC1 restricts the induced expression of these markers. We sought to identify specfic gene targets of ZXDC1 during the process of monocyte/macrophage differentiation in U937 by performing gene expression profiling in cells exhibiting reduced expression of ZXDC1 compared to controls.
The zinc finger transcription factor ZXDC activates CCL2 gene expression by opposing BCL6-mediated repression.
Specimen part, Cell line
View SamplesHuman genetic studies have identified the neuronal RNA binding protein, Rbfox1, as a candidate gene for autism spectrum disorders. While Rbfox1 functions as a splicing regulator in the nucleus, it is also alternatively spliced to produce cytoplasmic isoforms. To investigate cytoplasmic Rbfox1, we knocked down Rbfox proteins in mouse neurons and rescued with cytoplasmic or nuclear Rbfox1. Transcriptome profiling showed that nuclear Rbfox1 rescued splicing changes induced by knockdown, whereas cytoplasmic Rbfox1 rescued changes in mRNA levels. iCLIP-seq of subcellular fractions revealed that in nascent RNA Rbfox1 bound predominantly to introns, while cytoplasmic Rbox1 bound to 3'' UTRs. Cytoplasmic Rbfox1 binding increased target mRNA stability and translation, and overlapped significantly with miRNA binding sites. Cytoplasmic Rbfox1 target mRNAs were enriched in genes involved in cortical development and autism. Our results uncover a new Rbfox1 regulatory network and highlight the importance of cytoplasmic RNA metabolism to cortical development and disease. In this data set, we included the data from RNA-seq experiments. Overall design: We performed RNA-seq to profile gene expression and splicing changes. The expression levels of Rbfox1 and Rbfox3 in cultured mouse hippocampal neurons were reduced by siRNAs. The reduction of Rbfox1 and 3 was rescued by expression of cytoplasmic or nuclear Rbfox1 splice isoform. The gene expression and splicing profiles were compared between different treatments. Eight samples were analyzed.
Cytoplasmic Rbfox1 Regulates the Expression of Synaptic and Autism-Related Genes.
No sample metadata fields
View SamplesThis study was aimed at elucidating the mechanisms underlying activity-dependent gene regulation during LTP of mouse hippocampal CA3-CA1 synapses. Deep sequencing of the 3' end of transcripts allowed to identify changes in APA induced 1 hour and 3 hours after LTP induction. We detected APA changes that only affected the 3''UTR (3''UTR-APA events) and APA changes that also affected the coding sequence (CDS-APA events). Overall design: We performed 3' region extraction and deep sequencing (3''READS) of acute hippocampal slices 1 hour and 3 hours after LTP induction, and of time-matched control slices. Hippocampal slices were prepared from 2-3 month old C57BL/6 wild-type mice, the dentate gyrus was trimmed, and the slices were placed in interface chambers to recover for 2 hours with continuous ACSF perfusion. From the same animal, half of the mini-slices were used for LTP induction (using a pharmacological protocol, cLTP) and the remaining slices were treated with a DMSO vehicle solution as controls. We sequenced triplicates (samples 1-3) of controls and cLTP treated slices for the 1 hour and 3 hours time-point.
Activity-Dependent Regulation of Alternative Cleavage and Polyadenylation During Hippocampal Long-Term Potentiation.
Age, Specimen part, Cell line, Subject
View SamplesRegulatory T cells (Treg cells) expressing the forkhead family transcription factor Foxp3 are critical mediators of dominant immune tolerance to self. Most Treg cells constitutively express the high-affinity interleukin 2 (IL-2) receptor alpha-chain (CD25); however, the precise function of IL-2 in Treg cell biology has remained controversial. To directly assess the effect of IL-2 signaling on Treg cell development and function, we analyzed mice containing the Foxp3gfp knock-in allele that were genetically deficient in either IL-2 (Il2-/-) or CD25 (Il2ra-/-). We found that IL-2 signaling was dispensable for the induction of Foxp3 expression in thymocytes from these mice, which indicated that IL-2 signaling does not have a nonredundant function in the development of Treg cells. Unexpectedly, Il2-/- and Il2ra-/- Treg cells were fully able to suppress T cell proliferation in vitro. In contrast, Foxp3 was not expressed in thymocytes or peripheral T cells from Il2rg-/- mice. Gene expression analysis showed that IL-2 signaling was required for maintenance of the expression of genes involved in the regulation of cell growth and metabolism. Thus, IL-2 signaling seems to be critically required for maintaining the homeostasis and competitive fitness of Treg cells in vivo.
A function for interleukin 2 in Foxp3-expressing regulatory T cells.
No sample metadata fields
View SamplesCombination therapy with estrogen and a selective estrogen receptor modulator (SERM) is a promising approach to safely alleviate important side effects related to estrogen deficiency in women at high risk for breast cancer. Data related to endometrial safety of estrogen+SERM co-therapies are limited, however. The primary goal of this study was to evaluate the endometrial profile of low-dose E2 and Tam alone and in combination.
Endometrial profile of tamoxifen and low-dose estradiol combination therapy.
No sample metadata fields
View SamplesComparison between two vegetative stages of the soybean cultivar BR16: 20 and 80 days after germination (DAG) Overall design: Examination of 2 vegetative stages: 20 and 80 DAGs
Revisiting the Soybean GmNAC Superfamily.
Age, Specimen part, Subject
View SamplesExamination of CD4+ T cells from Foxp3-GFP knock-in mice. Aim is to understand the genetic program governed by Foxp3 in T cells by comparison of CD4 T cells subdivided into four groups based on expression of Foxp3 and CD25.
Regulatory T cell lineage specification by the forkhead transcription factor foxp3.
No sample metadata fields
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Foxp3-dependent programme of regulatory T-cell differentiation.
Sex
View SamplesThe NOD (nonobese diabetic) mouse strain develops a characteristic autoimmune syndrome that closely resembles human type I diabetes. It has been suggested that NOD mice exhibit both numerical deficiency in CD4+CD25+ regulatory T cells (Treg) and reduced suppressive activity. We compared sorted CD4+CD25+ Tregs from the spleens of 6-7 week-old female NOD and nondiabetic B6.H2g7 mice. Tregs were 932% and 951% Foxp3+ in NOD and B6.H2g7 cells, respectively, on post-sort reanalysis. "Conventional" CD4+CD25- T cells (Tconv) are included as reference populations. Surprisingly, Treg "signature" is similar between the two strains, with only a few probesets that subtly deviate.
The defect in T-cell regulation in NOD mice is an effect on the T-cell effectors.
Age, Specimen part
View SamplesThis data set is comprised of all peripheral (pooled lymph nodes and spleen) T cell subsets presented in this manuscript. These include T-N, T-25, T-FN and T-R cells; T-25, T-FN and T-R cells from mice treated with IL-2; and T-R cells transduced with empty, PDE3B-expressing or PDE3B(H801A)-expressing retroviral vectors (after transfer into recipient mice).
Foxp3-dependent programme of regulatory T-cell differentiation.
Sex
View Samples