Metazoans utilize a handful of highly conserved signaling pathways to create a signaling backbone that governs all stages of development, by providing spatial and temporal cues that influence gene expression. How these few signals have such a versatile developmental action is of significance to evolution, development, and disease. Their versatility likely depends upon the larger-scale network they form through integration. Such integration is exemplified by cross-talk between the Notch and the Receptor Tyrosine Kinase (RTK) pathways. We examined the transcriptional output of Notch-RTK cross-talk during Drosophila development and present in vivo data that supports a role for selected mutually-regulated genes as potentially important nodal points for signal integration. We find the complex interplay between these pathways involves their mutual regulation of numerous core components of RTK signaling in addition to targets that include components of all the major signalling pathways (TGF-, Hh, Jak/Stat, Nuclear Receptor and Wnt). Interestingly, Notch-RTK integration did not lead to general antagonism of either pathway, as is commonly believed. Instead, integration had a combinatorial effect on specific cross-regulated targets, which unexpectedly included the majority of Ras-responsive genes, suggesting Notch can specify the response to Ras activation.
Nodal points and complexity of Notch-Ras signal integration.
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View SamplesUbiquitin Ligase (UBE4B) and Lysine-Specific Demethylase (LSD1) are post-translational modifying enzymes affecting lysine ubiquitination and methylation of several important regulatory proteins, and are synergisticaly important for protein quality control. To inwestigate their role in cell signaling, we analyzed global mRNA levels in HEK293T cells that were knocked down with shRNAs against UBE4B, LSD1, both UBE4B and LSD1, and non-targeting control (CTRL).
Regulation of protein quality control by UBE4B and LSD1 through p53-mediated transcription.
Cell line, Time
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Systems genetics identifies a co-regulated module of liver microRNAs associated with plasma LDL cholesterol in murine diet-induced dyslipidemia.
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View SamplesGenetic variation, in addition to environmental influences like diet, can govern the expression levels of microRNAs (miRNAs). MiRNAs are commonly found to operate cooperatively in groups to regulate gene expression. To investigate this, we combined small RNA sequencing, clinical phenotypes, and microarray data measuring gene expression from an outbred mouse model, the Diversity Outbred population. In the DO population, each individual has a distinct genome that is a mosaic of 8 inbred founder strains. We used these data to identify co-regulated modules of miRNAs and genes that are influenced by genetics and diet, and identify relationships between the modules and phenotypes in over 200 DO mice.
Systems genetics identifies a co-regulated module of liver microRNAs associated with plasma LDL cholesterol in murine diet-induced dyslipidemia.
No sample metadata fields
View SamplesApproximately, KSHV vIRF4 deregulate 284 genes by two-folds
Kaposi's sarcoma-associated herpesvirus viral interferon regulatory factor 4 (vIRF4) targets expression of cellular IRF4 and the Myc gene to facilitate lytic replication.
Cell line
View SamplesThe rate of cell differentiation is tightly controlled and critical for normal development and stem cell differentiation. However, so far it has been difficult to control the rate of ESCs differentiation. Here we report the acceleration of the differentiation rate due to the activation of protein kinase A (PKA) and the associated early loss of embryonic stem cells (ESCs) pluripotency markers and the early appearance of mesodermal and other germ layer cell markers.
Protein kinase A accelerates the rate of early stage differentiation of pluripotent stem cells.
Time
View SamplesIn the present study transcriptome and proteome of recombinant, xylose-utilising S. cerevisiae grown in aerobic batch cultures on xylose were compared with glucose-grown cells both in glucose repressed and derepressed states. The aim was to study at genome-wide level how signalling and carbon catabolite repression differed in cells grown on either glucose or xylose. The more detailed knowledge about is xylose sensed as a fermentable carbon source, capable of catabolite repression like glucose, or is it rather recognised as a non-fermentable carbon source is important in achieving understanding for further engineering this yeast for more efficient anaerobic fermentation of xylose.
Regulation of xylose metabolism in recombinant Saccharomyces cerevisiae.
No sample metadata fields
View SamplesIt is well-known that indomethacin (the cyclooxygenase 1 & 2 inhibitor) and RU486 (or mifepristone, the progesterone receptor antagonist) block follicular rupture in rats. To characterize genetic alterations in unruptured follicles, gene expression profiles in ovarian follicle were analyzed in indomethacin- and RU486-treated female Sprague-Dawley rats. Ovaries are collected at 22:00 on the proestrus day and 10:00 on the following estrus day after a single dose of indomethacin and RU486. Histopathologically, changes depicting responses to LH surge were observed in ovaries, uteri and vagina. Total RNA was extracted from pre-ovulatory follicles or unruptured follicles collected by laser microdissection and analyzed by GeneChip. Among genes showing statistically significant changes compared to control groups, following changes were considered relevant to induction of unruptured follicles. In indomethacin-treated rats, Wnt4 was down-regulated, suggesting effect on tissue integrity and steroid genesis. In RU486-treated rats, Adamts1, Adamts9, Edn2, Ednra, Lyve1, Plat, and Pparg were down-regulated. These changes suggest effects on proteolysis for extracellular matrix or surrounding tissue (Adamts1 & 9, and Plat), constriction of smooth muscle surrounding follicles (Edn2, Ednra, and Pparg), follicular fluid (Lyve1), and angiogenesis (Pparg). Down-regulation of angiogenesis related genes (Angpt2, Hmox1, and Vegfa) was observed in both treatment groups. Here, we clarify genetic alterations induced by the inhibition of cyclooxygenase or progesterone receptor.
Altered gene expression profile in ovarian follicle in rats treated with indomethacin and RU486.
Specimen part, Treatment
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Downregulation of ERG and FLI1 expression in endothelial cells triggers endothelial-to-mesenchymal transition.
Specimen part
View SamplesNegative-pressure wound therapy (NPWT) is widely used to improve skin wound healing and to accelerate wound bed preparation. Although NPWT has been extensively studied as a treatment for deep wounds, its effect on epithelialization of superficial dermal wounds remains unclear. To clarify the effect of NPWT on reepithelialization, we applied NPWT on split- thickness skin graft donor sites from the first postoperative day (POD) to the seventh POD. Six patients took part in the study and two samples were obtained from each. The first biopsy sample was taken at elective surgery before split-thickness skin grafting and the second one during reepithelialization on the seventh POD. In all 12 samples (eight from four NPWT patients, and four from two control patients) were collected for this study. From each sample, we carried out a comprehensive genome-wide microarray analysis. Data from patients receiving NPWT were compared groupwise with data from those not receiving NPWT.
Gene expression profiling of negative-pressure-treated skin graft donor site wounds.
Treatment, Subject
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