To understand the specific mechanism by which Foxj3 and Zbtb18 control RA-induced neural directional differentiation of ESCs, total mRNAs of Foxj3-ES and Zbtb18-ES were extracted and used for RNA seq and transcriptome analyses. Compared with the control, 1331 genes were differentially expressed (P < 0.05) by twofold in Foxj3-ES (557 were underexpressed and 774 were overexpressed), and 1175 genes were differentially expressed (P < 0.05) by twofold in Zbtb18-ESCs (548 were underexpressed and 627 were overexpressed). Through Gene ontology and gene co-expression network analysis, we identified four critical genes in the neural regulatory networks: Olig1, Zic5, Erbb2, and Olig2. Our study shows that Foxj3 and Zbtb18 could trigger the gene regulatory networks of neurodevelopment by mediating the expression of Olig1, Zic5, Erbb2, and Olig2. Overall design: mRNA profiles of Foxj3 or Zbtb18 stable expressed embryonic stem cell lines by deep sequencing
Retinoic acid-induced upregulation of miR-219 promotes the differentiation of embryonic stem cells into neural cells.
No sample metadata fields
View SamplesNeurofibromatosis type II (NF2) is a disease that needs new solutions. Vestibular schwannoma (VS) growth cause progressive hearing loss, and the standard treatment including surgery and radiotherapy, can further damage the nerve. There is an urgent need to identify an adjunct therapy that, by enhancing the efficacy of radiation, can help lower the radiation dose and preserve hearing. The mechanisms underlying deafness in NF2 are still unclear. One of the major limitations in studying tumor-induced hearing loss is the lack of mouse models that allows hearing test. Here we developed a cerebellopontine angle (CPA) schwannomas model that faithfully recapitulates the tumor-induced hearing loss. Using this model we discovered that cMET blockade by crizotinib (CRZ) enhanced schwannoma radiosensitivity by enhancing DNA damage, and CRZ treatment combined with low-dose radiation was as effective as high-dose radiation. CRZ treatment had no adverse effect on hearing; however, it did not affect tumor-induced hearing loss, presumably because cMET blockade did not change tumor HGF levels. cMET gene knockdown study independently confirmed the role of cMET pathway in mediating the effect of CRZ. Furthermore, we evaluated the translational potential of cMET blockade in human schwannomas. We found that human NF2-associated and sporadic VSs showed significantly elevated HGF expression and cMET activation compared to normal nerves, which correlated with tumor growth and cyst formation. Using organoid brain slice culture, cMET blockade inhibited the growth of patient-derived schwannomas. Our findings provide the rationale and necessary data for the clinical translation of combined cMET blockade with radiation therapy in NF2 patients.
Targeting the cMET pathway augments radiation response without adverse effect on hearing in NF2 schwannoma models.
Sex, Age, Specimen part, Disease, Disease stage
View SamplesIn the early zebrafish embryo, the developing genome profile can be interfered with by exposure to pentachlorophenol, and some specific sets of genes are up-regulated or down-regulated. We used microarrays to detail the global program of gene expression underlying cellularisation and identified distinct classes of up-regulated genes during this process.
Pentachlorophenol exposure causes Warburg-like effects in zebrafish embryos at gastrulation stage.
Specimen part, Treatment
View SamplesDiabetic nephropathy(DN) is a common diabetic microvascular complication, the underlying mechanisms involved in DN remain to be elucidated.
Transcriptional Profile of Kidney from Type 2 Diabetic db/db Mice.
Sex, Age, Specimen part
View SamplesWe analyzed three clinical parameters with gene expression data from 122 liver tissues. Six healthy samples were used in validation.
Predictive model for inflammation grades of chronic hepatitis B: Large-scale analysis of clinical parameters and gene expressions.
Specimen part
View SamplesAs the leading cause of food-borne illness in the world, Salmonella have evolved a sophisticated machinery to alter host cell function to promote virulence and survival.In this study, we compare production of non-coding RNAs between Salmonella-infected cells and mock infection cells. Using Solexa deep sequencing, we detected a panel of 19-24nt Salmonella-derived non-coding RNA fragments with considerable large copy numbers in human colonic epithelial HT-29 cells following Salmonella infection.The fragment with the highest copy number, Sal-1, was further validated by both quantitative reverse transcription polymerase chain reaction (qRT-PCR) and northern blot. The generation of Sal-1 requires the infection of host cells by Salmonella, and the processing of the Sal-1 “primary” or “precursor” to the mature Sal-1 in Salmonella-infected cells is Dicer-independent but Argonaute 2 (Ago2)-dependent. Functionally, Sal-1 suppresses the expression of colonic epithelial cell endogenous inducible nitric oxide synthase (iNOS) via targeting its open reading frame and thus reduces the bacterial resistance of host cells. Overall design: Screening and identification of Salmonella-encoded microRNA-like RNA fragments
Salmonella produce microRNA-like RNA fragment Sal-1 in the infected cells to facilitate intracellular survival.
No sample metadata fields
View SamplesMammalian circadian rhythm is established by the negative feedback loops consisting of a set of clock genes, which lead to the circadian expression of thousands of downstream genes. As genome-wide transcription is organized under the high-order chromosome structure, it is unclear how circadian gene expression is influenced by chromosome structure. In this study, we focus on the function of chromatin structure proteins cohesin as well as CTCF (CCCTC-binding factor) in circadian rhythm. We analyzed the interactome of a Bmal1-bound enhancer upstream of a clock gene, Nr1d1, by 4C-seq and observed that cohesin binding sites are enriched in the interactome. Integrating circadian transcriptome data and cistrome data, we found that cohesin-CTCF co-binding sites tend to insulate the phases of circadian oscillating genes while cohesin-non-CTCF sites facilitate the interaction between circadian enhancer and promoter. A coarse-grained model integrating the long-range effect of cohesin and CTCF markedly improved our mechanistic understanding of circadian gene expression. This model is subsequently supported by our RNA-seq data from cohesin knockout cells. Cohesin is required at least in part for driving the circadian gene expression by facilitating the enhancer-promoter looping. Taken together, our study provided a novel insight into the relationship between circadian transcriptome and the high-order chromosome structure. Overall design: RNA-Seq in WT and Smc3-/- mouse embryonic fibroblast cells
Long-Range Chromosome Interactions Mediated by Cohesin Shape Circadian Gene Expression.
No sample metadata fields
View SamplesCG3875 is a young duplicate gene of kep1 family originated recently in Drosophila melanogaster (D. melanogaster) species complex (including D. melanogaster, D. simulans, D. mauritiana and D. sechellia) after it split from D. yakuba. It encodes an RNA-binding protein containing a single maxi-KH domain. Characterization of loss-of-function phenotypes of CG3875 mutants generated by gene targeting demonstrated that CG3875 null males display a seriously reduced fertility compared with wildtype males and most of the null males are completely sterile. Further cytological identification of CG3875 null males suggested that CG3875 plays an important role in spermiogenesis processes including sperm individualization and sperm coiling. In addition, CG3875 is also essential for the formation of outer dynein arm of sperm axoneme. In order to identify the molecular mechanism responsible for the involvement of CG3875 in spermiogenesis and structural integrity of sperm axoneme, we performed microarray analysis to identify transcripts whose levels are altered in the testes of CG3875 null males.
A young Drosophila duplicate gene plays essential roles in spermatogenesis by regulating several Y-linked male fertility genes.
Sex, Specimen part
View SamplesIllumina/Solexa sequencing of CG3985 mutant and wildtype testes transcriptome (0-1 day males)
A young Drosophila duplicate gene plays essential roles in spermatogenesis by regulating several Y-linked male fertility genes.
No sample metadata fields
View SamplesWe performed a zebrafish forward genetic screen by Tol2 mediated gene-trap approach and uncovered one mutant stac (The number of the transgenic line: B55) that showed severe cell-death distributed in the various brain and trunk in the homozygote embryos. Analysis of stac homozygous embryos demonstrates typical apoptosis. So it is necessary to analyze whether the apoptosis and cell cycle regulated signaling transductions are changed in the mutant, in order to provide valuable clues to some other species. And the up-regulated and down-regulated genes in the mutant compared to the WT were examined by zebrafish cDNA microarray.
Interruption of cenph causes mitotic failure and embryonic death, and its haploinsufficiency suppresses cancer in zebrafish.
Treatment
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