We used microarrays to detail the global programme of gene expression dependent upon Stat3 in regulatory T cells
CD4+ regulatory T cells control TH17 responses in a Stat3-dependent manner.
Sex, Specimen part
View SamplesThe adult mammalian brain is composed of distinct regions that have specialized roles. To dissect molecularly this complex structure, we conducted a project, named the BrainStars (B*) project, in which we sampled ~50 small brain regions, including sensory centers and centers for motion, time, memory, fear, and feeding. To avoid confusion from temporal differences in gene expression, we sampled each region every 4 hours for 24 hours, and pooled the sample sets for DNA-microarray assays. Therefore, we focused only on spatial differences in gene expression. We then used informatics to identify candidates for (1) genes with high or low expression in specific regions, (2) switch-like genes with bimodal or multimodal expression patterns, and (3) genes with a uni-modal expression pattern that exhibit stable or variable levels of expression across brain regions. We used our findings to develop an integrated database (http://brainstars.org/) for exploring genome-wide expression in the adult mouse brain.
Quantitative expression profile of distinct functional regions in the adult mouse brain.
Sex, Specimen part
View SamplesLiving organisms detect seasonal changes in day length (photoperiod), and alter their physiological functions accordingly, to fit seasonal environmental changes. This photoperiodic system is implicated in seasonal affective disorders and the season-associated symptoms observed in bipolar disease and schizophrenia. Thyroid-stimulating hormone beta subunit (Tshb), induced in the pars tuberalis (PT), plays a key role in the pathway that regulates animal photoperiodism. However, the upstream inducers of Tshb expression remain unknown. Here we show that late-night light stimulation acutely triggers the Eya3-Six1 pathway, which directly induces Tshb expression. Using melatonin-proficient CBA/N mice, which preserve the photoperiodic Tshb-expression response, we performed a genome-wide expression analysis of the PT under chronic short-day and long-day conditions. These data comprehensively identified long-day and short-day genes, and indicated that late-night light stimulation induces long-day genes. We verified this by advancing and extending the light period by 8 hours, which acutely induced Tshb expression, within one day. In a genome-wide expression analysis under this condition, we searched for candidate upstream genes by looking for expression that preceded Tshbs, and identified Eya3 gene. These results elucidate the comprehensive transcriptional photoperiodic response in the PT, revealing the complex regulation of Tshb expression and unexpectedly rapid response to light changes in the mammalian photoperiodic system.
Acute induction of Eya3 by late-night light stimulation triggers TSHβ expression in photoperiodism.
Sex, Age, Specimen part, Time
View SamplesRecognition and response to gram-positive bacteria by macrophages and dendritic cells is mediated in part through TLR2. We found that that Streptococcus pneumoniae cell wall fragments, containing primarily peptidoglycan and teichoic acids, induced prodigious secretion of IL-10 from macrophages and dendritic cells and was dependent on TLR2 and NOD2, a cytoplasmic CARD-NACHT-LRR protein encoded by Card15. IL-10 secretion in response to cell walls was also dependent on RICK/RIP2, a kinase associated with NOD2, and MYD88 but independent of the ERK/p38 pathway. The reduction of IL-10 secretion by cell wall-activated NOD2-deficient myeloidderived cells translated into downstream effects on IL-10 target gene expression and elevations in subsets of pro-inflammatory cytokine expression normally restrained by autocrine/paracrine effects of IL-10. Since NOD2 is linked to aberrant immune responses in Crohns Disease patients bearing mutations in CARD15, the temporal and quantitative effects of the TLR2/NOD/RICK pathway on IL-10 secretion may affect homeostatic control of immune responses to gram-positive bacteria.
The TLR2-MyD88-NOD2-RIPK2 signalling axis regulates a balanced pro-inflammatory and IL-10-mediated anti-inflammatory cytokine response to Gram-positive cell walls.
No sample metadata fields
View SamplesOsteosarcoma (OS) is the malignant bone tumor with a high tendency to metastasize to the lung, where the molecular mechanisms are unclear. The mouse OS cell line LM8 has been isolated originally from the Dunn OS cell line by in vivo selection as a subline with a high metastatic potential to the lung.
Stable knockdown of S100A4 suppresses cell migration and metastasis of osteosarcoma.
Cell line
View SamplesCellular signal transduction is governed by multiple feedback mechanisms to elicit robust cellular decisions. We combined mathematical modeling and extensive time-resolved data sets in primary erythroid progenitor cells and dissected the roles of the two transcriptional feedback regulators of the SOCS family, CIS and SOCS3 in JAK2/STAT5 signaling. Our model revealed that both feedbacks are most effective at different ligand concentration ranges.
Division of labor by dual feedback regulators controls JAK2/STAT5 signaling over broad ligand range.
Specimen part
View SamplesXBP1 is the transcriptino factor that is activated by the ER stress. XBP1 is known to induce the ER dexpansion and increase the expression of the ER chaperone genes to prtect the cell from the ER stress. We generated a mouse strain that lacked XBP1 specifically in the mouse intestine by breeding the XBP1flox mice with Villin-cre mice. Here we examined genes that are differentially expressed between WT and XBP1 KO mouse intestine to identify genes that are downstream of XBP1.
XBP1 links ER stress to intestinal inflammation and confers genetic risk for human inflammatory bowel disease.
No sample metadata fields
View SamplesThe Toll-like receptor 4 (TLR4) pathway is important for tumor-initiating cells. We used microarrays to obtain gene profiling data in order to increase understanding of the pathways.
Reciprocal regulation by TLR4 and TGF-β in tumor-initiating stem-like cells.
Sex, Specimen part
View SamplesProper functioning of tissues requires cells to behave in uniform, well-organized ways. Conversely, many diseases involve increased cellular heterogeneity due to genetic and epigenetic alterations. Defining the mechanisms that counteract phenotypic variability is therefore critical to understand how tissues sustain homeostasis. Here, we carried out a single-cell resolution screen of zebrafish embryonic blood vessels upon mutagenesis of single microRNA (miRNA) genes and multi-gene miRNA families. We found that miRNA mutants exhibit a profound increase in cellular phenotypic variability of specific vascular traits. Genome-wide analysis of endothelial miRNA target genes identified antagonistic regulatory nodes of vascular growth and morphogenesis signaling that allow variable cell behaviors when derepressed. Remarkably, lack of such miRNA activity greatly sensitized the vascular system to microenvironmental changes induced by pharmacological stress. We uncover a previously unrecognized role of miRNAs as a widespread protective mechanism that limits variability in cellular phenotypes. This discovery marks an important advance in our comprehension of how miRNAs function in the physiology of higher organisms. Overall design: Analysis of differential genes expression in Zebrafish endothelial cells for 4 different developmental stages
MicroRNAs Establish Uniform Traits during the Architecture of Vertebrate Embryos.
No sample metadata fields
View SamplesDN3, DN4 and DP cells were sorted from 3-4 week old WT and mice and subjected to transcriptome analysis
The tumor suppressor Ikaros shapes the repertoire of notch target genes in T cells.
Specimen part
View Samples