NetSciReg'13 - Network Models in Cellular Regulation
June 4, 2013 - Copenhagen

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Global Epigenetic State Network Governs Cellular Pluripotent
Reprogramming and Transdifferentiation

Chaoming Song, Ping Wang, Hang Zhang, Zhanghan Wu,
Xiao-Jun Tian, Jianhua Xing

Time: 2:50 - 3:15 PM

Type: Contributed talk

Affiliation: Northeastern University, USA

Abstract

Recent breakthroughs of cell phenotype reprogramming impose theoretical challenge on unravelling the complexity of large circuits maintaining cell phenotypes coupled at many different epigenetic and gene regulation levels, and quantitatively describing the phenotypic transition dynamics. A popular picture proposed by Waddington views cell differentiation as a ball sliding down a landscape with valleys corresponding to different cell types separated by ridges. Based on theories of dynamical systems we establish a novel "epigenetic state network" framework that captures the global architecture of cell phenotypes, which allows us to translate the metaphorical low-dimensional Waddington's epigenetic landscape concept into a simple-yet-predictive rigorous mathematical framework of cell phenotypic transitions. Specifically, we simplify a high dimensional epigenetic landscape into a collection of discrete states corresponding to stable cell phenotypes connected by optimal transition pathways among them. We then apply the approach to the reprogramming process of fibroblasts to induced pluripotent stem cells (iPSC) and cardiomyocytes, and correctly predict intermediate states and multiple reprogramming pathways, which are supported by existing microarray data and other experiments. New experiments are further suggested. Chaoming Song - Graphical Abstract


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