Project description:Tryptophan treatment play a significant role in miR expression. We have characterized the miR expression network through miR-on-chip profiling of the mouse treated with or without tryptophan. In this dataset, we include the expression data from mouse small intestine and colon tissue treated with or without tryptophan.
Project description:Tryptophan treatment play a significant role in miR expression. We have characterized the miR expression network through miR-on-chip profiling of the mouse treated with or without tryptophan. In this dataset, we include the expression data from mouse small intestine and colon tissue treated with or without tryptophan.
Project description:Tryptophan metabolism and de novo NAD biosynthesis is associated with behavioural changes in IBD patients. The microbiota and tryptophan de novo syntheses of the distal colon, distal colon and brain of C57BL/6 control mice and Winnie mice littermates with chronic intestinal inflammation were compared using RNA-Seq. Differentially expressed genes were analysed using Micromon software. Changes in tryptophan and nicotinamide metabolism-associated gene expressions, metabolites, and abundance of gut microbiota associated with chronic intestinal inflammation and dysregulated tryptophan metabolism in the Winnie mouse distal colon and brain were apparent. Our findings shed light on the physiological alterations in tryptophan metabolism, specifically its diversion from the serotonergic pathway towards the kynurenine pathway and the consequential effects on de novo NAD+ synthesis, in the context of chronic intestinal inflammation
Project description:Essential amino acids (EAA) and microRNAs (miRs) control biological activity of a cell. Whether EAA regulates the activity of miR has never been demonstrated. Here, as proof-of-concept, a tryptophan (Trp, an EAA) complex containing Argonaute 2 (Ago2) and miRs including miR-193a (Trp/Ago2/miR-193a) is identified. Trp binds miR-193a-3p and interacts with Ago2. Trp/Ago2/miR-193a increases miR-193a-3p activity via enhancing Argonaute 2 (Ago2) RNase activity. Other miRs including miR-103 and miR-107 in the Trp complex enhance miR-193a activity by targeting the same genes. Mechanistically, the Trp/Ago2/miR-193a complex interacts with Trp-binding pockets of the PIWI domain of Ago2 to enhance Ago2 mediated miR activity. This newly formed Ago2/Trp/miR-193a-3p complex is more efficient than miR-193a-3p alone in inhibiting the expression of targeted genes and inhibiting colon cancer liver metastasis. The findings show that Trp regulates miR activity through communication with the RNA-induced silencing complexes (RISC), which provides the basis for tryptophan based miR therapy.
Project description:In the experimental autoimmune encephalomyelitis (EAE) model we found that omission of the essential amino acid tryptophan (trp) abrogates central nervous system (CNS) autoimmunity. Impaired encephalitogenic T responses were accompanied by an inflammatory response in the colonic mucosa, as well as a profound shift in the gut microbiota. Here, we performed transcriptional profiling of colon tissue by RNA-sequencing 14 days after disease induction in mice that received a trp-free diet or a matched control group to identify key networks that drive this immunosuppressive effect.
Project description:Studies of the Xenopus organizer have laid the foundation for our understanding of the conserved signaling pathways that pattern vertebrate embryos during gastrulation. Here, we use this wealth of knowledge as leverage in the design and analysis of a genomic visualization of organizer-related gene transcription. Using ectopic expression of the two major activities of the organizer, BMP and Wnt inhibition, as well as endogenous tissues, we generate a focused set of samples that represent different aspects of organizer signaling. The genomic expression values of each sample are then measured with oligonucleotide arrays. From this data, genes regulated by organizer signaling are selected and then clustered by their patterns of regulation. A new GO biological process annotation of the Xenopus genome allows us to rapidly identify clusters that are highly enriched for known gastrula patterning genes. Within these clusters, we can predict the expression patterns of unknown genes with remarkable accuracy, leading to the discovery of new organizer-related gastrula stage expression patterns for 19 genes. Moreover, the patterns of gene response observed within these clusters allow us to parse apart the contributions of BMP and Wnt inhibition in organizer function. We find that the majority of gastrula patterning genes respond transcriptionally to these activities according to only a few stereotyped patterns, allowing us to describe suites of genes that are likely to share similar regulatory mechanisms. These suites of genes demonstrate a mechanism where BMP inhibition initiates the organizer program before gastrulation, and Wnt inhibition maintains and drives the organizer program during gastrulation. Keywords: development, organizer, noggin, dkk-1, xenopus, gastrulation
Project description:Recapitulation of development in vitro relies primarily on treatment of progenitor cells with media-borne morphogens, without the complex spatial instructions normally presented by native developmental niches. Here we build simple spatially asymmetric developmental niches by engineering synthetic organizer cells that self-assemble around stem cells and provide spatially-defined morphogenic instructions. Using a toolkit of natural and engineered adhesion molecules we harness differential adhesion to program the formation of specific organizer cell geometries around the stem cells, allowing the generation of morphogen gradients with tunable position, amplitude, and signal types. Synthetic niches presenting the antagonistic morphogens WNT3A and DKK1 were used to guide development of pluripotent stem cells. These synthetic organizers generated distinct morphological outcomes, including formation of a beating heart-like chamber and embryoids containing a complement of diverse cell lineages derived from mesoderm, endoderm and ectoderm. The resulting morphologies were reproducible in high-throughput format. Spatially programmable synthetic organizer cells, which integrate the principles of differential adhesion and positional information, thus provide a systematic approach to guide, recapitulate, and modify development in a controlled fashion.
Project description:Eosinophilia–myalgia syndrome (EMS) is characterized by subacute onset of myalgias and peripheral eosinophilia, followed by chronic neuropathy and skin induration. The EMS epidemic in 1989 was linked to L-tryptophan consumption originating from a single source. Following the Food and Drug Administration (FDA) ban on the sale of L-tryptophan, the incidence of EMS declined rapidly. Moreover, no new cases have been published since the FDA ban was lifted in 2005. We report the clinical, histopathological and immunogenetic features of a new case of L-tryptophan-associated EMS along with evidence of activated transforming growth factor-ß and interleukin-4 signaling in the lesional skin. 6 samples were analyzed to include EMS patient and two replicates along with three normal controls