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Please use this identifier to cite or link to this item: http://ntour.ntou.edu.tw:8080/ir/handle/987654321/40178

Title: Stochastic Simulation of Notch Signaling Reveals Novel Factors That Mediate the Differentiation of Neural Stem Cells
Authors: Wen-Shyong Tzou
Ying-Tsang Lo
Tun-Wen Pai
Chin-Hwa Hu
Chung-Hao Li
Contributors: 國立臺灣海洋大學:資訊工程學系
Keywords: stochastic processes
biochemical networks
computational molecular biology
gene networks
Date: 2014
Issue Date: 2017-01-16T03:09:37Z
Publisher: J Comput Biol
Abstract: Abstract: Notch signaling controls cell fate decisions and regulates multiple biological processes, such as cell proliferation, differentiation, and apoptosis. Computational modeling of the deterministic simulation of Notch signaling has provided important insight into the possible molecular mechanisms that underlie the switch from the undifferentiated stem cell to the differentiated cell. Here, we constructed a stochastic model of a Notch signaling model containing Hes1, Notch1, RBP-Jk, Mash1, Hes6, and Delta. mRNA and protein were represented as a discrete state, and 334 reactions were employed for each biochemical reaction using a graphics processing unit–accelerated Gillespie scheme. We employed the tuning of 40 molecular mechanisms and revealed several potential mediators capable of enabling the switch from cell stemness to differentiation. These effective mediators encompass different aspects of cellular regulations, including the nuclear transport of Hes1, the degradation of mRNA (Hes1 and Notch1) and protein (Notch1), the association between RBP-Jk and Notch intracellular domain (NICD), and the cleavage efficiency of the NICD. These mechanisms overlap with many modifiers that have only recently been discovered to modulate the Notch signaling output, including microRNA action, ubiquitin-mediated proteolysis, and the competitive binding of the RBP-Jk-DNA complex. Moreover, we identified the degradation of Hes1 mRNA and nuclear transport of Hes1 as the dominant mechanisms that were capable of abolishing the cell state transition induced by other molecular mechanisms.
Relation: 21(7)
URI: http://ntour.ntou.edu.tw:8080/ir/handle/987654321/40178
Appears in Collections:[資訊工程學系] 期刊論文

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