Several Toll-like receptors are activated by Listeria monocytogenes infection, resulting in the activation of MyD88 dependent signaling pathway. However, the negative role of MyD88 in gene expresson is unclear.
Beneficial innate signaling interference for antibacterial responses by a Toll-like receptor-mediated enhancement of the MKP-IRF3 axis.
Specimen part
View SamplesTargeted differentiation of human induced pluripotent stem cells (hiPSCs) using only chemicals is proclaimed to have value-added clinical potential in the regeneration of complex cell types like cardiomyocytes. Despite the availability of several small molecule inhibitors capable of modulating specific receptor-ligand interaction or enzymatic activity, no bioactive synthetic DNA-binding inhibitor targeting key cell fate-controlling gene like SOX2 is available yet. Herein, we demonstrate a novel DNA-based chemical approach to guide hiPSCs differentiation using pyrrole-imidazole polyamides (PIPs), which are sequence-selective DNA-binding synthetic molecules. Harnessing the knowledge about key transcriptional changes associated with cardiomyocyte induction, we developed a PIP termed SOX-L targeting 5-CTTTGTT-3 sequence and demonstrate the inhibition of SOX2-DNA interaction and mesoderm induction of hiPSCs. Genome-wide gene analyses revealed that SOX-L remarkably specified cardiac mesoderm by triggering targeted alteration in SOX2-associated gene regulatory networks. Also, employment of SOX-L along with a Wnt inhibitor successfully generated spontaneously contracting cardiomyocytes to validate our concept that DNA-binding inhibitors like PIPs could be used for directed differentiation of hiPSCs. Because PIPs could be fine-tuned to target specific DNA sequences, our DNA-based approach could be expanded to directly target and distinctively regulate key transcription factor associated with the desired cell type.
A synthetic DNA-binding inhibitor of SOX2 guides human induced pluripotent stem cells to differentiate into mesoderm.
Specimen part, Cell line, Treatment, Time
View SamplesThe Golgi stress response is a homeostatic mechanism that augments the functional capacity of the Golgi apparatus when Golgi function becomes insufficient (Golgi stress). Three response pathways of the Golgi stress response have been identified in mammalian cells, the TFE3, HSP47 and CREB3 pathways, which augment the capacity of specific Golgi functions such as N-glycosylation, anti-apoptotic activity and pro-apoptotic activity, respectively. On the contrary, glycosylation of proteoglycans (PGs) is another important function of the Golgi, although the response pathway upregulating expression of glycosylation enzymes for PGs in response to Golgi stress remains unknown. Here, we found that expression of glycosylation enzymes for PGs was induced upon insufficiency of PG glycosylation capacity in the Golgi (PG-Golgi stress), and that transcriptional induction of genes encoding glycosylation enzymes for PGs was independent of the known Golgi stress response pathways and ER stress response. Promoter analyses of genes encoding these glycosylation enzymes revealed the novel enhancer element PGSE, which regulates their transcriptional induction upon PG-Golgi stress. From these observations, the response pathway we discovered is a novel Golgi stress response pathway, which we have named the PG pathway. Overall design: Three control samples (DMSO-treated) and three 4MU-xyloside-treated samples
PGSE Is a Novel Enhancer Regulating the Proteoglycan Pathway of the Mammalian Golgi Stress Response.
Sex, Specimen part, Cell line, Treatment, Subject
View SamplesA gene expression profile of BRCAness was defined in publicly available expression data of 61 patients with epithelial ovarian cancer (34 patients with BRCA-1 or BRCA-2 mutations and 27 patients with sporadic disease). This dataset is publicly available at http://jnci.oxfordjournals.org/cgi/content/full/94/13/990/DC1
Gene expression profile of BRCAness that correlates with responsiveness to chemotherapy and with outcome in patients with epithelial ovarian cancer.
Age, Disease stage
View SamplesEndothelial cells (Ecs) lining the blood vessels have been known to have a variety of functions and play a central role in homeostasis of the circulatory system.
Transcription profiles of endothelial cells in the rat ductus arteriosus during a perinatal period.
Specimen part
View SamplesWe report the differences in gene expression between wild type and Tgif1;Tgif2 double null mouse embryos at approximately 9.0 days after fertilization. Overall design: Stage matched individual mouse embryos at approximately 9.0 days after fertilization (~9-10 somites) were analyzed by RNA-seq. We analyzed four wild type embryos and eight conditional double mutant embryos, lacking both alleles of Tgif1 and both Tgif2 alleles.
Tgif1 and Tgif2 Repress Expression of the RabGAP Evi5l.
Age, Specimen part, Subject
View SamplesAcquisition of a new strain of non-typeable Haemophilus influenzae (NTHi) is often associated with exacerbation of chronic obstructive pulmonary disease (COPD). We have previously reported that COPD patients who are homozygous null for SIGLEC14 gene is less susceptible to COPD exacerbation than those who have wild-type allele with functional SIGLEC14 gene.
Association of serum interleukin-27 with the exacerbation of chronic obstructive pulmonary disease.
Cell line
View SamplesPyrrole-imidazole polyamides (PIPs) have been shown to inhibit gene expression by interrupting the DNA-protein interface. Human Ectopic viral integration site 1 (EVI1) is an oncogenic transcription factor which plays a key role in many aggressive forms of cancer. We have developed a novel pyrroleimidazole polyamide, PIP1 targeting the REL/ELK1 binding site in the EVI1 minimal promoter that can significantly repress the expression of EVI1 in MDA-MB-231 cells. Whole-transcriptome analysis revealed that a fraction of EVI1-driven genes were modulated by PIP1.
Targeted suppression of EVI1 oncogene expression by sequence-specific pyrrole-imidazole polyamide.
Specimen part, Cell line
View SamplesSphingomyelin synthase (SMS) 2 is the synthetic enzyme of sphingomyelin (SM), which regulates the fluidity and microdomain structure of the plasma membrane. We investigated the effect of SMS2 deficiency on dextran sodium sulfate (DSS)-induced murine colitis, and found suppression of DSS-induced inflammation in SMS2 deficient (SMS2-/-) mice. Results provide insight into the role of SMS2 in inflammation.
Sphingomyelin synthase 2 deficiency inhibits the induction of murine colitis-associated colon cancer.
Specimen part, Treatment
View SamplesTo identify regulation of genes involved in lipid and glycogen metabolism by PGC-1alpha
Suppression of PGC-1α Is Critical for Reprogramming Oxidative Metabolism in Renal Cell Carcinoma.
Specimen part, Cell line
View Samples