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10.1371/journal.pcbi.1005400 http://scihub22266oqcxt.onion/10.1371/journal.pcbi.1005400 C5363986!5363986!28245235     free     free     free Deprecated: Implicit conversion from float 227.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 227.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 227.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 227.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 227.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534       PLoS+Comput+Biol 2017 ; 13 (2): ä Nephropedia Template TP {{tp|p=28245235|t=2017. The role of the Hes1 crosstalk hub in Notch-Wnt interactions of the intestinal crypt |pdf=|usr=}}{{28245235}} gab.com Text The role of the Hes1 crosstalk hub in Notch-Wnt interactions of the intestinal crypt JO: PLoS Comput Biol http://www.kidney.de/pget.php?&tw=1&pmid=28245235 #FOAvip The Notch pathway plays a vital role in determining whether cells in the intestinal epithelium adopt a secretory or an absorptive phenotype. Cell fate specification is coordinated via Notch?s interaction with the canonical Wnt pathway. Here, we propose a new mathematical model of the Notch and Wnt pathways, in which the Hes1 promoter acts as a hub for pathway crosstalk. Computational simulations of the model can assist in understanding how healthy intestinal tissue is maintained, and predict the likely consequences of biochemical knockouts upon cell fate selection processes. Chemical reaction network theory (CRNT) is a powerful, generalised framework which assesses the capacity of our model for monostability or multistability, by analysing properties of the underlying network structure without recourse to specific parameter values or functional forms for reaction rates. CRNT highlights the role of ?-catenin in stabilising the Notch pathway and damping oscillations, demonstrating that Wnt-mediated actions on the Hes1 promoter can induce dynamic transitions in the Notch system, from multistability to monostability. Time-dependent model simulations of cell pairs reveal the stabilising influence of Wnt upon the Notch pathway, in which ?-catenin- and Dsh-mediated action on the Hes1 promoter are key in shaping the subcellular dynamics. Where Notch-mediated transcription of Hes1 dominates, there is Notch oscillation and maintenance of fate flexibility; Wnt-mediated transcription of Hes1 favours bistability akin to cell fate selection. Cells could therefore regulate the proportion of Wnt- and Notch-mediated control of the Hes1 promoter to coordinate the timing of cell fate selection as they migrate through the intestinal epithelium and are subject to reduced Wnt stimuli. Furthermore, mutant cells characterised by hyperstimulation of the Wnt pathway may, through coupling with Notch, invert cell fate in neighbouring healthy cells, enabling an aberrant cell to maintain its neighbours in mitotically active states. Twit Text FOAVip The role of the Hes1 crosstalk hub in Notch-Wnt interactions of the intestinal crypt ????PLoS Comput Biol http://www.kidney.de/pget.php?&tw=1&pmid=28245235 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=28245235 #FOAvip English Wikipedia <ref>{{Cite pmid|28245235}}</ref> The role of the Hes1 crosstalk hub in Notch-Wnt interactions of the intestinal crypt #MMPMID28245235 Kay SK; Harrington HA; Shepherd S; Brennan K; Dale T; Osborne JM; Gavaghan DJ; Byrne HM PLoS Comput Biol 2017[Feb]; 13 (2): ä PMID28245235show ga The Notch pathway plays a vital role in determining whether cells in the intestinal epithelium adopt a secretory or an absorptive phenotype. Cell fate specification is coordinated via Notch?s interaction with the canonical Wnt pathway. Here, we propose a new mathematical model of the Notch and Wnt pathways, in which the Hes1 promoter acts as a hub for pathway crosstalk. Computational simulations of the model can assist in understanding how healthy intestinal tissue is maintained, and predict the likely consequences of biochemical knockouts upon cell fate selection processes. Chemical reaction network theory (CRNT) is a powerful, generalised framework which assesses the capacity of our model for monostability or multistability, by analysing properties of the underlying network structure without recourse to specific parameter values or functional forms for reaction rates. CRNT highlights the role of ?-catenin in stabilising the Notch pathway and damping oscillations, demonstrating that Wnt-mediated actions on the Hes1 promoter can induce dynamic transitions in the Notch system, from multistability to monostability. Time-dependent model simulations of cell pairs reveal the stabilising influence of Wnt upon the Notch pathway, in which ?-catenin- and Dsh-mediated action on the Hes1 promoter are key in shaping the subcellular dynamics. Where Notch-mediated transcription of Hes1 dominates, there is Notch oscillation and maintenance of fate flexibility; Wnt-mediated transcription of Hes1 favours bistability akin to cell fate selection. Cells could therefore regulate the proportion of Wnt- and Notch-mediated control of the Hes1 promoter to coordinate the timing of cell fate selection as they migrate through the intestinal epithelium and are subject to reduced Wnt stimuli. Furthermore, mutant cells characterised by hyperstimulation of the Wnt pathway may, through coupling with Notch, invert cell fate in neighbouring healthy cells, enabling an aberrant cell to maintain its neighbours in mitotically active states. äThe role of the Hes1 crosstalk hub in Notch-Wnt interactions of the in(epmc).pdf DeepDyve Pubget Overpricing