The goal was to identify targets of the RNase REGE-1 by whole RNA sequencing. Overall design: mRNA profiling of C.elegans young adults of rege-1 knockdown or mock RNAi control performed in N2 as well as glp-1 background
Ribonuclease-Mediated Control of Body Fat.
Cell line, Subject
View SamplesEts-4 was previously identified as a suppressor of rege-1(rrr13) phenotype. The goal of this experiment was to identify down-stream regulators of ETS-4, which facilitate this suppression. Overall design: mRNA profiling of C.elegans young adults of ets-4 knockdown or mock RNAi control in the background of rege-1(rrr13)
Ribonuclease-Mediated Control of Body Fat.
Cell line, Subject
View SamplesWe compared the transcriptomes of EpiSCs maintained in the presence or absence of Wnt pathway inhibitor IWP2. We screened also our gene expression data for potential markers for genuine EpiSCs, maintained in the presence of Wnt inhibition and compared with ESC expression data. We compared the transcriptomes of EpiSCs maintained in the presence or absence of IWP2. The high level of Wnt-induced differentiation occurring in conventional EpiSC cultures may have interfered with the analysis of their characteristics. By applying Wnt inhibitors we are now able to establish the properties of genuine EpiSCs.
Endogenous WNT signals mediate BMP-induced and spontaneous differentiation of epiblast stem cells and human embryonic stem cells.
Specimen part, Treatment
View SamplesThe first HSCs are produced in the aorta-gonadmesonephros (AGM) region of the embryo through endothelial to a hematopoietic transition. BMP4 and Hedgehog affect their production/expansion, but it is unknown whether they act to affect the same HSCs. In this study using the BRE GFP reporter mouse strain that identifies BMP/Smad-activated cells, we find that the AGM harbors two types of adult-repopulating HSCs upon explant culture. Overall design: Embryonic day 11 AGM are dissected and either analyzed directly, or after explant culture in conditions containing BMP/Hedgehog with or without cyclopamine. EC: endothelial enriched (CD31+Kit-); MC: mesenchymal cell enriched (CD31-Kit-); HPSC: hematopoietic progenitor/stem cell enriched; AGM11: E11 fresh AGMs; AGMex: AGM after explant culture; AGMcy: AGM after explant in presence of cyclopamine; CD31p: CD31 positive; CD31n: CD31 negative; KITp: c-Kit positive; KITn: c-Kit negative; BREp: BRE-GFP positive; BREn: BRE-GFP negative
BMP and Hedgehog Regulate Distinct AGM Hematopoietic Stem Cells Ex Vivo.
Specimen part, Cell line, Subject
View SamplesWe used RNA-Seq to analyse the interactions between Bmp4 and Wnt at a genome-wide level in EpiSCs treated for 48 hrs with Bmp4 and/or Wnt3a in the presence of Activin and bFGF. Overall design: Control EpiSC were cultured in the presence of IWP2 for 48h. Cells were cultured with BMP4 with or without IWP2; Wnt3a and Wnt3a with BMP4 for 48h.
Endogenous WNT signals mediate BMP-induced and spontaneous differentiation of epiblast stem cells and human embryonic stem cells.
No sample metadata fields
View SamplesInadequate extracellular conditions can adversely affect the environment of the ER and impinge on the maturation of nascent proteins. The resultant accumulation of unfolded proteins activates a signal transduction pathway, known as the unfolded protein response, which serves primarily to protect the cell during stress and helps restore homeostasis to the ER. Microarray analysis of the unfolded protein response in a human medulloblastoma cell line treated with thapsigargin revealed that, in addition to known targets, a large number of proangiogenic factors were up-regulated. Real-time PCR analyses confirmed that four of these factors, VEGF, FGF2, angiogenin and IL-8, were transcriptionally up-regulated in multiple cell lines by various ER stress inducers. Our studies on VEGF regulation revealed that XBP-1(S), a UPR-inducible transcription factor, bound to two regions on the VEGF promoter, and analysis of XBP-1 null mouse embryonic fibroblasts revealed that it contributes to VEGF expression in response to ER stress. ATF4, another UPR-inducible transcription factor, also binds to the VEGF gene, although its contribution to VEGF transcription appeared to be fairly modest. We also found that VEGF mRNA stability is increased in response to UPR activation, via activation of the AMP and p38MAP kinases, demonstrating that increased mRNA levels occur at two regulatory points. In keeping with the mRNA levels, we found that VEGF protein is secreted at levels as high as or higher than that achieved in response to hypoxia. Our results indicate that the UPR plays a significant role in inducing positive regulators of angiogenesis. It also regulates VEGF expression at multiple levels and is likely to have widespread implications for promoting angiogenesis in response to normal physiological cues as well as in pathological conditions like cancer.
Transcriptional and post-transcriptional regulation of proangiogenic factors by the unfolded protein response.
Treatment, Time
View SamplesInnate immune sensing of influenza A virus (IAV) induces activation of various immune effector mechanisms including the NLRP3 inflammasome and programmed cell death pathways. Although type I IFNs are identified as key mediators of inflammatory and cell death responses during IAV infection, the involvement of various IFN-regulated effectors in facilitating these responses are less studied. Here, we demonstrate the role of interferon regulatory factor 1 (IRF1) in promoting NLRP3 inflammasome activation and cell death during IAV infection. IRF1 functions as a transcriptional regulator of Z-DNA binding protein 1 (ZBP1, also called as DLM1/DAI), a key molecule mediating IAV-induced inflammatory and cell death responses. Therefore, our study identified IRF1 as an upstream regulator of NLRP3 inflammasome and cell death during IAV infection and further highlights the complex and multilayered regulation of key molecules controlling inflammatory response and cell fate decisions during infections.
IRF1 Is a Transcriptional Regulator of ZBP1 Promoting NLRP3 Inflammasome Activation and Cell Death during Influenza Virus Infection.
Specimen part
View SamplesLoss of Pggt1b leads to marked defects in thymocyte egress and T cell lymphopenia in peripheral lymphoid organs in vivo
Mevalonate metabolism-dependent protein geranylgeranylation regulates thymocyte egress.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Hippo/Mst signaling coordinates cellular quiescence with terminal maturation in iNKT cell development and fate decisions.
Specimen part, Disease
View SamplesIL-10 regulates anti-inflammatory signaling via the activation of STAT3, which in turn controls the induction of a gene expression program whose products execute inhibitory effects on pro-inflammatory mediator production. Here we show that IL-10 induces the expression of an ETS family transcriptional repressor, ETV3 and a helicase family co-repressor, SBNO2 (Strawberry notch homolog 2) in mouse and human macrophages. IL-10-mediated induction of ETV3 and SBNO2 expression was dependent upon both STAT3, and co-stimulus through the TLR pathway. We also observed that ETV3 expression was strongly induced by the STAT3 pathway induced by IL-10 but not STAT3 signaling activated by IL-6, which cannot activate the anti-inflammatory signaling pathway. ETV3 and SBNO2 specifically repressed NF-kB-mediated transcription and can physically interact. Collectively our data suggest that ETV3 and SBNO2 are components of the pathways that contribute to the downstream anti-inflammatory effects of IL-10.
Cutting edge: A transcriptional repressor and corepressor induced by the STAT3-regulated anti-inflammatory signaling pathway.
No sample metadata fields
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