The object of this study was to identify genes transcriptionally upregulated and downregulated in response to Tcof1 haploin-sufficiency during mouse embryogensis
Prevention of the neurocristopathy Treacher Collins syndrome through inhibition of p53 function.
No sample metadata fields
View SamplesRegulation of lineage specification and differentiation in embryonic stem (ES) cells can be achieved through the activation of endogenous signaling, an avenue for potential application in regenerative medicine. During vertebrate development, retinoic acid (RA) plays an important role in body axis elongation and mesoderm segmentation in that graded exposure to RA provides cells with positional identity and directs commitment to specific tissue lineages. We have previously established that bexarotene, a clinically approved rexinoid, enhances the specification and differentiation of ES cells into skeletal myocytes more effectively than RA. Profiling the transcriptomes of ES cells differentiated with bexarotene or RA permits the identification of different genetic targets and signaling pathways that may contribute to the difference of bexarotene and RA in efficiency of myogenesis. Interestingly, bexarotene induces the early expression of a myogenic progenitor marker, Meox1, while the expression of many RA targets is also enhanced by bexarotene. Several signaling molecules involved in the progression of myogenic specification and commitment are differentially regulated by bexarotene and RA, suggesting that early targets of rexinoids allow the coordinated regulation of molecular events which leads to efficient myogenic differentiation in ES cells.
Gene expression profiling discerns molecular pathways elicited by ligand signaling to enhance the specification of embryonic stem cells into skeletal muscle lineage.
Specimen part, Treatment, Time
View SamplesBackground: Cardiac transcription factors are master regulators during heart development. Recently, some were shown to transdifferentiate noncardiac mesoderm cells and cardiac fibroblasts into cardiomyocytes. However, the individual roles of each transcription factors in activating cardiac gene program have not been elucidated. We examined cardiac-specific and genome-wide gene expression in fibroblasts induced with cardiac transcription factors Nkx2.5 (N), Tbx5 (T), Gata4 (G), Myocardin (M) alone or different combinations.
Cardiac gene activation analysis in mammalian non-myoblasic cells by Nkx2-5, Tbx5, Gata4 and Myocd.
Cell line
View SamplesIdentification of genes differentially expressed in roots of Arabidopsis Col-0 and ndr1-1 mutants 48 h post inoculation with the fungal pathogen Verticillium longisporum.
Susceptibility to Verticillium longisporum is linked to monoterpene production by TPS23/27 in Arabidopsis.
Age, Specimen part, Time
View SamplesIn the present investigation, we have exploited the opportunity provided by neoadjuvant treatment of a group of postmenopausal women with large operable or locally advanced breast cancer (in which therapy is given with the primary tumour remaining within the breast) to take sequential biopsies of the same cancers before and after 10-14 days or 90 days treatment with letrozole. RNA extracted from the biopsies has been subjected to Affymetrix microarray analysis and the data from paired biopsies interrogated to discover genes whose expression is most influenced by oestrogen deprivation.
Sequential changes in gene expression profiles in breast cancers during treatment with the aromatase inhibitor, letrozole.
Sex, Specimen part, Subject, Time
View SamplesPurpose: Evaluate gene expression profiles after inducing differentiation in cultured interstitial cystitis (IC) and control urothelial cells. Materials and Methods: Bladder biopsies were taken from IC patients and controls (women having surgery for stress incontinence). Primary cultures were grown in Keratinocyte Growth Medium with supplements. To induce differentiation, in some plates the medium was changed to DMEM-F12 with supplements. RNA was analyzed with Affymetrix chips. Three nonulcer IC patients were compared with three controls. Results: After inducing differentiation, 302 genes with a described function were altered at least 3-fold with p <0.01 in both IC and control cells. Functions of the162 upregulated genes included cell adhesion (e.g. claudins, occludin, cingulin); urothelial differentiation, retinoic acid pathway and keratinocyte differentiation (e.g. skin cornified envelope components). The 140 downregulated genes included genes associated with basal urothelium (e.g. p63, integrins ?4, ?5 and ?6, basonuclin 1 and extracellular matrix components), vimentin, metallothioneins and members of the Wnt and Notch pathways. Comparing IC vs. control cells after differentiation, only seven genes with a described function were altered at least 3-fold with p <0.01. PI3, SERPINB4, CYP2C8, EFEMP2 and SEPP1 were decreased in IC; AKR1C2 and MKNK1 were increased in IC. Conclusions: Differentiation-associated changes occurred in both IC and control cells. Comparing IC vs. control revealed very few differences. This study may have included IC patients with minimal urothelial deficiency and/or selected the cells that were most robust in culture. Also, the abnormal urothelium in IC may be due to post-translational changes and/or the bladder environment.
Differentiation associated changes in gene expression profiles of interstitial cystitis and control urothelial cells.
Disease
View SamplesWild type Arabidopsis thaliana Col-0 root cultures, were treated with fenclorim or 4-chloro-6-methyl-2-phenylpyrimidine dissolved in acetone to achieve a final concentration of 100uM. The final acetone concentration of 0.1% was replicated in control root cultures. Samples were taken at four and twenty-four hours post addition in biological triplicate. Root cultures were routinely maintained at 25C in the dark.
Xenobiotic responsiveness of Arabidopsis thaliana to a chemical series derived from a herbicide safener.
Specimen part
View SamplesKarrikins promote seed germination in Arabidopsis thaliana. Completion of germination (protrusion of the radicle) is not observed until ~72 h in dormant wildtype seed under these conditions. We used microarrays to examine karrikin-induced transcriptional changes after 24 h of imbibition. Transcriptional changes may indicate events leading to karrikin-induced germination or karrikin-specific markers.
Karrikins enhance light responses during germination and seedling development in Arabidopsis thaliana.
Specimen part, Treatment
View SamplesThe innate immune system is vital to rapidly responding to pathogens and Toll-like receptors (TLRs) are a critical component of this response. Nanovesicular exosomes play a role in immunity, but to date their exact contribution to the dissemination of the TLR response is unknown. To understand the effect of exosomal cargo released from locally stimulated cells on distal cell expression, we collected exosomes from local ovarian adenocarcinoma (HEY) cells that were either unstimulated (control-exosomes), stimulated with pIC (pIC-exosomes), or lipopolysaccharide (LPS-exosomes) for 48 hours. The three groups of exosomes were added to nave (distal) cells and the gene expression profiles were compared between local TLR stimulation (for 6 hours) and distal stimulation mediated by exosomes at the 48-hour time point
TLR-exosomes exhibit distinct kinetics and effector function.
Specimen part, Cell line, Treatment
View SamplesWhile skeletal myogenesis is tightly coordinated by myogenic regulatory factors including MyoD and myogenin, chromatin modifications have emerged as vital mechanisms of myogenic regulation. We have previously established that bexarotene, a clinically approved agonist of retinoid X receptor, promotes the specification and differentiation of skeletal muscle lineage. Here, we examine a genome-wide impact of rexinoids on myogenic differentiation through integral RNA-seq and ChIP-seq analyses. We found that bexarotene promotes myoblast differentiation through the coordination of exit from the cell cycle and the activation of muscle-related genes. We uncovered a new mechanism of rexinoid action which is mediated by the nuclear receptor and largely reconciled through a direct regulation of MyoD gene expression. In addition, we determined a rexinoid-responsive residue-specific histone acetylation at a distinct chromatin state associated to MyoD and myogenin. Thus, we provide novel molecular insights into the interplay between retinoid X receptor signaling and chromatin states pertinent to myogenic programs in early myoblast differentiation. Overall design: We have profiled the global effect of bexarotene, a selective agonist of retinoid X receptor on myoblast gene expression by RNA-seq analysis using RNA isolated from C2C12 myoblasts following 12 or 24 hours of differentiation in the presence and absence of 50 nM bexarotene, with 2 biological replicates. Proliferating myoblasts were used as controls.
Insights into interplay between rexinoid signaling and myogenic regulatory factor-associated chromatin state in myogenic differentiation.
Cell line, Subject
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