Inflammasome activation is critical for host defense against various microbial infections. Activation of the NLRC4 inflammasome requires detection of flagellin or type III secretion system (T3SS) components by NLR family apoptosis inhibitory proteins (NAIPs); yet how this pathway is regulated is unknown. Here we found that interferon regulatory factor 8 (IRF8) is required for optimal activation of the NLRC4 inflammasome in bone marrow-derived macrophages infected with Salmonella Typhimurium, Burkholderia thailandensis, or Pseudomonas aeruginosa but is dispensable for activation of the canonical and non-canonical NLRP3, AIM2, and Pyrin inflammasomes. IRF8 governs the transcription of Naips to allow detection of flagellin or T3SS proteins to mediate NLRC4 inflammasome activation. Furthermore, we found that IRF8 confers protection against bacterial infection in vivo, owing to its role in inflammasome-dependent cytokine production and pyroptosis. Altogether, our findings suggest that IRF8 is a critical regulator of NAIPs and NLRC4 inflammasome activation for defense against bacterial infection.
IRF8 Regulates Transcription of Naips for NLRC4 Inflammasome Activation.
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View SamplesGene expression profiling to determine transcriptome changes following Snail or Slug expression in MCF-7 breast cancer cells
The transcription factors Snail and Slug activate the transforming growth factor-beta signaling pathway in breast cancer.
Cell line, Treatment
View SamplesThe basic helix-loop-helix factor Myod initiates skeletal muscle differentiation by directly and sequentially activating sets of muscle differentiation genes, including those encoding muscle contractile proteins. We hypothesize that Pbx homeodomain proteins direct Myod to a subset of its transcriptional targets, in particular fast twitch muscle differentiation genes, thereby regulating the competence of muscle precursor cells to differentiate. We have previously shown that Pbx proteins bind with Myod on the promoter of the zebrafish fast muscle gene mylpfa and that Pbx proteins are required for Myod to activate mylpfa expression and the fast-twitch muscle-specific differentiation program in zebrafish embryos. Here we have investigated the interactions of Pbx with another muscle fiber-type regulator, Prdm1a, a SET-domain DNA-binding factor that directly represses mylpfa expression and fast muscle differentiation. The prdm1a mutant phenotype, early and increased fast muscle differentiation, is the opposite of the Pbx-null phenotype, delayed and reduced fast muscle differentiation. To determine whether Pbx and Prdm1a have opposing activities on a common set of genes, we used RNA-seq analysis to globally assess gene expression in zebrafish embryos with single- and double-losses-of-function for Pbx and Prdm1a. We find that the levels of expression of certain fast muscle genes are increased or approximately wild type in pbx2/4-MO;prdm1a-/- embryos, suggesting that Pbx activity normally counters the repressive action of Prdm1a for a subset of the fast muscle program. However, other fast muscle genes require Pbx but are not regulated by Prdm1a. Thus, our findings reveal that subsets of the fast muscle program are differentially regulated by Pbx and Prdm1a. Our findings provide an example of how Pbx homeodomain proteins act in a balance with other transcription factors to regulate subsets of a cellular differentiation program. Overall design: Total RNA samples were genotyped and pooled for 4 sample types: control-MO;prdm1+/+; control-MO;prdm1-/-; pbx2/4-MO;prdm1+/+; and pbx2/4-MO;prdm1-/- embryos at the 10 somite (s) stage from three independent sets of egg collections/injections.
Pbx and Prdm1a transcription factors differentially regulate subsets of the fast skeletal muscle program in zebrafish.
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View SamplesIn this dataset we include the data obtained from 3 hour stimulation with Neisseria gonorrhoeae (GC) of bone marrow macrophages(BMDM) from wild type (C57BL/6) and Nod2 knock out mice (in C57BL/6 background).
Activation of NOD receptors by Neisseria gonorrhoeae modulates the innate immune response.
Specimen part
View SamplesAssessment of the putative differential gene expression profiles in high osmolality-treated bovine nucleus pulposus intervertebral disc cells for a short (5 h) and a long (24 h) time period. Identification of novel genes up- or down-regulated as an early or a late response to hyperosmotic stress.
Deficiency in the α1 subunit of Na+/K+-ATPase enhances the anti-proliferative effect of high osmolality in nucleus pulposus intervertebral disc cells.
Specimen part
View SamplesThe Ets2 transcription factor is essential for the development of the mouse placenta and for generating signals for embryonic mesoderm and axis formation. Using a conditional targeted Ets2 allele, we show that Ets2 is essential for trophoblast stem (TS) cells self renewal. Inactivation of Ets2 results in slower growth, increased expression of a subset of differentiation associated genes and decreased expression of several genes implicated in TS self renewal. Among the direct TS targets of Ets2 is Cdx2, a key master regulator of TS cell state. In addition other Ets2 responsive genes include Pace4, Errb, Socs2 and Bmp4. Thus Ets2 contributes to the regulation of multiple genes important for maintaining the undifferentiated state of TS cells and as candidate signals for embryonic development.
Ets2 is required for trophoblast stem cell self-renewal.
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View SamplesPbx homeodomain proteins have been implicated in the regulation of gene expression during muscle development. Whether Pbx proteins are required broadly for the regulation of muscle gene expression or are required for the expression of a specific subset of muscle gene expression is not known. We employed microarrays to determine the requirements for Pbx proteins during zebrafish development.
Pbx homeodomain proteins direct Myod activity to promote fast-muscle differentiation.
No sample metadata fields
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Role of CD34 antigen in myeloid differentiation of human hematopoietic progenitor cells.
No sample metadata fields
View SamplesComparison of dorsal skin gene expression between GFP and IL-17 gene transfer in C57BL/6J mice
T Cell-Independent Mechanisms Associated with Neutrophil Extracellular Trap Formation and Selective Autophagy in IL-17A-Mediated Epidermal Hyperplasia.
Specimen part
View SamplesIn order to investigate the role of CD34 antigen in haematopoietic commitment, we overexpressed the human CD34 cDNA in human CD34+ cells by retroviral gene transfer.
Role of CD34 antigen in myeloid differentiation of human hematopoietic progenitor cells.
No sample metadata fields
View Samples