Tumor necrosis factor receptor associated factor 6 (TRAF6) is an adaptor protein that regulates NF-B and MAPK signaling pathway and is reported to affect immune response and cell death in immune cells. However, the roles of TRAF6 in epithelium have not been well investigated. Using a mouse model of imiquimod-induced psoriasis dermatitis, we show that TRAF6 in epithelial cells totally regulates IL-17-mediated inflammation in the skin. Mice lacking TRAF6 in keratinocytes were unable to activate dendritic cells and failed to produce IL-23 or initiate IL-17 production from T cells at the imiquimod-treated sites. Subcutaneous administrations of IL-23 restored IL-17 production in the mutant animals, suggesting that the induction of IL-23 production is the major TRAF6-dependent contribution of keratinocytes to this process. Therefore, the epithelial TRAF6 signaling is supposed to play an essential role in instructing and propagating the cutaneous immune response.
Epithelial TRAF6 drives IL-17-mediated psoriatic inflammation.
Sex, Age, Specimen part
View SamplesRNA-seq was used to assess mRNA transcript abundance in wild type and fra2? S. cerevisiae (BY4741) cells treated with 2-(6-benzyl-2-pyridyl)quinazoline (BPQ) and CuSO4. BPQ potentiates copper toxicity and in yeast, in common with other organisms, a major cause of copper toxicity is damage of iron-sulphur clusters. Iron sensing within yeast relies on mitochondrial iron-sulphur cluster biosynthesis and therefore treatment with BPQ and copper can be used to mimic iron deficiency. Fra2 is known to be a key component of the iron sensing mechanism; however, this mechanism can operate, to an extent, independently of Fra2. BPQ (+CuSO4) treatment was used with the aim of probing the regulation of the iron regulon of S. cerevisiae and the role of Fra2 in the suppression of the low iron response. This study has uncovered nine new Cth2 target-transcripts, plus a new Aft1 target-gene and paralogous non-target. Fra2 dominates basal repression of the iron regulon in iron-replete cultures, however, Fra2-independent control of the iron regulon is also observed with CTH2 appearing to be atypically Fra2-dependent. Transcripts from untreated and CuSO4 treated cells were included as controls. Overall design: Three independent biological replicates were analysed for each condition (BPQ and CuSO4 treated wild type and fra2? cells, CuSO4 treated wild type and fra2? cells and untreated wild type and fra2? cells)
A chemical potentiator of copper-accumulation used to investigate the iron-regulons of Saccharomyces cerevisiae.
Cell line, Treatment, Subject
View SamplesChromatin modifying activities for construction of appropriate epigenetic landscapes by polycomb repressive complex 2 (PRC2) play an essential role in development and tumorigenesis. However, the spatiotemporal mechanisms by which PRC2 achieves diverse epigenomes for specific tissue or cellular contexts remain poorly understood. Here, we discovered that LATS2 knockout causes dysregulation of PRC2 and subsequent transcriptome changes for differentiation in both mouse and human cells. LATS2 depletion dependent dysregulation of PRC2 also effects H3K4me3 and forms negative feedback loop for maintenance of PRC2. Further analyses reveal that LATS2 on chromatin binds to EZH2 and LATS2 has ability to phosphorylate PRC2 in vitro. These LATS2 dependent H3K27me3 targets are highly induced during neurogenesis, and statistical analysis of glioblastoma multiforme reveals that LATS2-high cases show more dedifferentiated transcriptome and poor prognosis with silencing of H3K27me3 targets. These observations suggest that LATS2-mediated epigenome coordination is pivotal for development and disease, including cancer. Overall design: mRNA of LATS2 KO HeLa-S3 cells rescued by empty vector, wild-type LATS2 or kinase-dead LATS2 were subjected to deep sequencing profiling using Illumina HiSeq 2500
LATS2 Positively Regulates Polycomb Repressive Complex 2.
No sample metadata fields
View SamplesTo investigate the expression characteristic of miRNAs during the development of Down syndrome (DS) fetuses and to identify whether another miRNA gene resides in the Hsa21, we employed high-throughput Solexa sequencing technology to comprehensively characterize the miRNA expression profiles of both DS and normal fetal cord blood mononuclear cells (CBMCs). In total, 200 of 395 identified miRNAs were significantly differentially expressed (fold change > 2.0 and P-value < 0.001) and 2 of 181 candidate novel miRNAs were identified as residing within the "Down syndrome critical region" of human chromosome 21 (chr21q22.2-22.3). Additionally, 7 of 14 Hsa21-derived miRNAs genes were detected that three miRNAs (hsa-miR-802, miR-3648, miR-3687) were up-regulated more than 50% and four miRNAs (hsa-miR-99a, let-7c, miR-125b-2, miR-155) were down-regulated in the DS fetal CBMCs compared with the control. Bioinformatics analyses revealed that abnormally expressed miRNAs were major associated with the regulation of transcription, gene expression, cellular biosynthetic process, macromolecule biosynthetic process and nucleic acid metabolic process. The data obtained in our study provides a considerable insight into understanding the expression characteristic of miRNAs in the DS fetal hemopoietic system and the differentially expressed miRNAs may be involved in the hemopoietic abnormalities and the immune defects of DS fetus and newborns. Overall design: A total of 6 DS and 6 matched control fetal cord blood samples (18-22 weeks of gestation) were collected. Three DS and 3 control cord blood samples were combined to form pooled DS and control cord blood samples, respectively, for small RNA library construction and Solexa sequencing. The remaining samples were used as the validation set to confirm the miRNA differential expression patterns by qRT-PCR.
Analysis of microRNA expression profile by small RNA sequencing in Down syndrome fetuses.
Specimen part, Disease, Subject
View SamplesPsoriasis is a chronic inflammatory skin disease related to immune, whose complexity of molecular mechanisms is still not fully clear. RNA sequencing has been widely applied in various fields including biological medicine. According to the bioinformatics analysis of differential genes, biomarkers and drug targets have been discovered for the diagnosis and treatment of diseases. Besides, the pathological mechanisms of disease and functions of gene can be evaluated. In the present study, we report the application of RNA sequencing in skin tissues from psoriatic and healthy persons. By obtaining 2139 differential expressed genes (DEGs), 208 significantly differential GO terms and 44 significantly differential pathways were generated. We found that the functions of DEGs were mainly related to cell cycle, inflammatory, virus, immune response and metabolic process.The major pathways included cytokine-cytokine receptor interaction, Toll-like receptor signaling pathway, chemokine signaling pathway, cell cycle, metabolic pathways, ribosome, peroxisome, steroid biosynthesis and biosynthesis of unsaturated fatty acids. Furthermore, co-expression network was constructed to identify core genes and relations between genes. we considered genes with high values of degree and k-core difference in the co-expression network as core genes, such as IFNG, IL26, TLR3, PRKCQ, TLR4, CD274, CDK1 and IL17A. We chose CD274, an important immune checkpoint, to evaluate its regulatory mechanisms. Candidate genes related to CD274 were evaluated by the co-expression network analysis, and the relations between CD274 and candidate genes were validated in epidermal keratinocytes. Finally, IFNG and CDK1 inhibitor (indirubin) were found increasing the expression levels of CD274. In addition, indirubin was confirmed to attenuate mouse psoriasis-like skin lesion with the mechanisms related to CD274. In conclusion, this study provides us a comprehensive transcriptome analysis method on psoriasis to identify core genes and explore the important regulatory functions of genes. Overall design: Nine normal skins from healthy volunteers and 18 lesional skins from patients with psoriasis vulgaris were obtained for RNA sequencing
Indirubin attenuates mouse psoriasis-like skin lesion in a CD274-dependent manner: an achievement of RNA sequencing.
Sex, Specimen part, Subject
View SamplesTrypanosoma cruzi is an obligate intracellular protozoan parasite that causes human Chagas disease, a leading cause of heart failure in Latin America. Using Affymetrix oligonucleotide arrays we screened phenotypically diverse human cells (foreskin fibroblasts, microvascular endothelial cells and vascular smooth muscle cells) for a common transcriptional response signature to T. cruzi. A common feature was a prominent type I interferon response, indicative of a secondary response to secreted cytokines. Using transwell plates to distinguish cytokine-dependent and -independent gene expression profiles in T. cruzi-infected cells, a core cytokine-independent response was identified in fibroblasts and endothelial cells that featured metabolic and signaling pathways involved in cell proliferation, amino acid catabolism and response to wounding. Significant downregulation of genes involved in mitotic cell cycle and cell division predicted that T. cruzi infection impedes cell cycle progression in the host cell.
Cytokine-dependent and-independent gene expression changes and cell cycle block revealed in Trypanosoma cruzi-infected host cells by comparative mRNA profiling.
No sample metadata fields
View SamplesExpression profile for undifferentiated F9 Embryonal Carcinoma cell line
Identification of active transcriptional regulatory modules by the functional assay of DNA from nucleosome-free regions.
No sample metadata fields
View SamplesMicroarray analysis was performed to identify transcriptional changes that occur during mucociliary differentiation of human primary bronchial epithelial cells cultured at an air-liquid interface (ALI).
Transcriptional profiling of mucociliary differentiation in human airway epithelial cells.
No sample metadata fields
View SamplesSkin-mammary specific knockout (SSKO) of Pygo2 (K14-cre; Pygo2 flox/-) , a WNT signaling co-activator, results in defective mouse mammary gland development.
Chromatin effector Pygo2 mediates Wnt-notch crosstalk to suppress luminal/alveolar potential of mammary stem and basal cells.
Specimen part
View SamplesDocetaxel is an adjuvant chemotherapy drug widely used to treat multiple solid tumors, however its toxicity and side-effect limits its clinical efficacy. Herein, the docetaxel-loaded solid lipid nanoparticles (DSNs) were developed to reduce systemic toxicity while still keeping its anti-cancer activity. To evaluate its anti-cancer activity and toxicity and understand the molecular mechanisms of DSNs, different cellular, molecular and whole genome transcription analysis approaches were utilized. The DSNs showed lower cytotoxicity compared with the commercial formulation of docetaxel-Taxotere and induced more apoptosis at 24 h treatment in vitro. It can cause the treated cancer cells arrested at G2/M phase in a dose-depend manner as Taxotere. The DSNs can also suppress tumor growth very effectively in a murine breast cancer model. Systemic analysis of gene expression profiles by microarray and the following verification experiments suggested that both DSNs and Taxotere regulate expression of series genes and these genes functions involved in DNA replication, DNA damage response, cell proliferation, apoptosis and cell cycle regulation. Some of these genes expressed differentially at protein level although their transcription level was similar under TAX and DSNs treatment. Moreover, DSNs improved main side-effect of Taxotere by greatly lowering myelosuppression toxicity to bone marrow cells from mice. Taken together, our results expound the anti-tumor efficacy and the potential working mechanisms of DSNs in its anti-cancer activity and toxicity, which provide a theoretical foundation to develop and apply more efficient docetaxel formulation to treat cancer patients.
Docetaxel-loaded solid lipid nanoparticles suppress breast cancer cells growth with reduced myelosuppression toxicity.
Specimen part
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