02975nas a2200313   4500008004100000022001400041245008300055210006900138260000900207300001100216490000600227520199700233653001202230653003302242653001102275653001702286653000902303653001802312653004402330653002502374653001902399653002702418100001902445700001902464700002002483700002002503700002002523856011802543       2012                        eng d  a1932-620300aExtensive translatome remodeling during ER stress response in mammalian cells.0 aExtensive translatome remodeling during ER stress response in ma  c2012  ae359150 v73 a<p>In this work we have described the translatome of two mammalian cell lines, NIH3T3 and Jurkat, by scoring the relative polysome association of ∼10,000 mRNA under normal and ER stress conditions. We have found that translation efficiencies of mRNA correlated poorly with transcript abundance, although a general tendency was observed so that the highest translation efficiencies were found in abundant mRNA. Despite the differences found between mouse (NIH3T3) and human (Jurkat) cells, both cell types share a common translatome composed by ∼800-900 mRNA that encode proteins involved in basic cellular functions. Upon stress, an extensive remodeling in translatomes was observed so that translation of ∼50% of mRNA was inhibited in both cell types, this effect being more dramatic for those mRNA that accounted for most of the cell translation. Interestingly, we found two subsets comprising 1000-1500 mRNA whose translation resisted or was induced by stress. Translation arrest resistant class includes many mRNA encoding aminoacyl tRNA synthetases, ATPases and enzymes involved in DNA replication and stress response such as BiP. This class of mRNA is characterized by high translation rates in both control and stress conditions. Translation inducible class includes mRNA whose translation was relieved after stress, showing a high enrichment in early response transcription factors of bZIP and zinc finger C2H2 classes. Unlike yeast, a general coordination between changes in translation and transcription upon stress (potentiation) was not observed in mammalian cells. Among the different features of mRNA analyzed, we found a relevant association of translation efficiency with the presence of upstream ATG in the 5'UTR and with the length of coding sequence of mRNA, and a looser association with other parameters such as the length and the G+C content of 5'UTR. A model for translatome remodeling during the acute phase of stress response in mammalian cells is proposed.</p>10aAnimals10aEndoplasmic Reticulum Stress10aHumans10aJurkat Cells10aMice10aNIH 3T3 Cells10aOligonucleotide Array Sequence Analysis10aProtein Biosynthesis10aRNA, Messenger10aTranscription, Genetic1 aVentoso, Iván1 aKochetov, Alex1 aMontaner, David1 aDopazo, Joaquin1 aSantoyo, Javier  uhttps://www.clinbioinfosspa.es/content/extensive-translatome-remodeling-during-er-stress-response-mammalian-cells02568nas a2200445   4500008004100000022001400041245010000055210006900155260001300224300001200237490000700249520111500256653001201371653002201383653003901405653002601444653002201470653004401492653001701536653003201553653000901585653002701594653005201621653002101673653002701694653001801721653003201739100002201771700001901793700001501812700002001827700002201847700001901869700002001888700002001908700002201928700002101950700002201971856012901993       2012                        eng d  a1530-686000aThe protease MT1-MMP drives a combinatorial proteolytic program in activated endothelial cells.0 aprotease MT1MMP drives a combinatorial proteolytic program in ac  c2012 Nov  a4481-940 v263 a<p>The mechanism by which proteolytic events translate into biological responses is not well understood. To explore the link of pericellular proteolysis to events relevant to capillary sprouting within the inflammatory context, we aimed at the identification of the collection of substrates of the protease MT1-MMP in endothelial tip cells induced by inflammatory stimuli. We applied quantitative proteomics to endothelial cells (ECs) derived from wild-type and MT1-MMP-null mice to identify the substrate repertoire of this protease in TNF-α-activated ECs. Bioinformatics analysis revealed a combinatorial MT1-MMP proteolytic program, in which combined rather than single substrate processing would determine biological decisions by activated ECs, including chemotaxis, cell motility and adhesion, and vasculature development. MT1-MMP-deficient ECs inefficiently processed several of these substrates (TSP1, CYR61, NID1, and SEM3C), validating the model. This novel concept of MT1-MMP-driven combinatorial proteolysis in angiogenesis might be extendable to proteolytic actions in other cellular contexts.</p>10aAnimals10aBlotting, Western10aCombinatorial Chemistry Techniques10aComputational Biology10aEndothelial Cells10aGene Expression Regulation, Enzymologic10aInflammation10aMatrix Metalloproteinase 1410aMice10aProtein Array Analysis10aReverse Transcriptase Polymerase Chain Reaction10aRNA Interference10aRNA, Small Interfering10aTranscriptome10aTumor Necrosis Factor-alpha1 aKoziol, Agnieszka1 aGonzalo, Pilar1 aMota, Alba1 aPollán, Angela1 aLorenzo, Cristina1 aColomé, Nuria1 aMontaner, David1 aDopazo, Joaquin1 aArribas, Joaquín1 aCanals, Francesc1 aArroyo, Alicia, G  uhttps://www.clinbioinfosspa.es/content/protease-mt1-mmp-drives-combinatorial-proteolytic-program-activated-endothelial-cells03591nas a2200649   4500008004100000022001400041245019000055210006900245260001600314300001200330490000700342520147500349653001801824653002201842653001201864653004901876653002501925653001401950653001701964653002101981653002502002653002002027653001902047653003002066653002902096653001102125653000902136653001802145653002802163653002802191653005202219653002902271653002402300653003002324653004802354653001802402100001402420700001802434700003002452700001602482700002002498700002002518700001702538700002402555700001902579700001902598700002802617700002002645700001902665700002802684700001802712700002202730700002002752700002002772700001902792856013002811       2011                        eng d  a1460-208300aLarge-scale transcriptional profiling and functional assays reveal important roles for Rho-GTPase signalling and SCL during haematopoietic differentiation of human embryonic stem cells.0 aLargescale transcriptional profiling and functional assays revea  c2011 Dec 15  a4932-460 v203 a<p>Understanding the transcriptional cues that direct differentiation of human embryonic stem cells (hESCs) and human-induced pluripotent stem cells to defined and functional cell types is essential for future clinical applications. In this study, we have compared transcriptional profiles of haematopoietic progenitors derived from hESCs at various developmental stages of a feeder- and serum-free differentiation method and show that the largest transcriptional changes occur during the first 4 days of differentiation. Data mining on the basis of molecular function revealed Rho-GTPase signalling as a key regulator of differentiation. Inhibition of this pathway resulted in a significant reduction in the numbers of emerging haematopoietic progenitors throughout the differentiation window, thereby uncovering a previously unappreciated role for Rho-GTPase signalling during human haematopoietic development. Our analysis indicated that SCL was the 11th most upregulated transcript during the first 4 days of the hESC differentiation process. Overexpression of SCL in hESCs promoted differentiation to meso-endodermal lineages, the emergence of haematopoietic and erythro-megakaryocytic progenitors and accelerated erythroid differentiation. Importantly, intrasplenic transplantation of SCL-overexpressing hESC-derived haematopoietic cells enhanced recovery from induced acute anaemia without significant cell engraftment, suggesting a paracrine-mediated effect.</p>10aAcute Disease10aAnemia, Hemolytic10aAnimals10aBasic Helix-Loop-Helix Transcription Factors10aCell Differentiation10aCell Line10aCell Lineage10aCluster Analysis10aEmbryonic Stem Cells10aErythroid Cells10aFlow Cytometry10aGene Expression Profiling10aHematopoietic Stem Cells10aHumans10aMice10aMyeloid Cells10aParacrine Communication10aProto-Oncogene Proteins10aReverse Transcriptase Polymerase Chain Reaction10arho GTP-Binding Proteins10aSignal Transduction10aStem Cell Transplantation10aT-Cell Acute Lymphocytic Leukemia Protein 110aTranscriptome1 aYung, Sun1 aLedran, Maria1 aMoreno-Gimeno, Inmaculada1 aConesa, Ana1 aMontaner, David1 aDopazo, Joaquin1 aDimmick, Ian1 aSlater, Nicholas, J1 aMarenah, Lamin1 aReal, Pedro, J1 aParaskevopoulou, Iliana1 aBisbal, Viviana1 aBurks, Deborah1 aSantibanez-Koref, Mauro1 aMoreno, Ruben1 aMountford, Joanne1 aMenendez, Pablo1 aArmstrong, Lyle1 aLako, Majlinda  uhttps://www.clinbioinfosspa.es/content/large-scale-transcriptional-profiling-and-functional-assays-reveal-important-roles-rho