Network Analysis Identifies Crosstalk Interactions Governing TGF-β Signaling Dynamics during Endoderm Differentiation of Human Embryonic Stem Cells
1
Department of Chemical and Petroleum Engineering, University of Pittsburgh, Pittsburgh, PA 15261, USA
2
Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA 15219, USA
3
McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, PA 15219, USA
*
Author to whom correspondence should be addressed.
Academic Editor: Juergen Hahn
Processes 2015, 3(2), 286-308; https://doi.org/10.3390/pr3020286
Received: 15 December 2014 / Revised: 29 March 2015 / Accepted: 24 April 2015 / Published: 4 May 2015
(This article belongs to the Special Issue Modeling and Analysis of Signal Transduction Networks)
Abstract
The fate choice of human embryonic stem cells (hESCs) is controlled by complex signaling milieu synthesized by diverse chemical factors in the growth media. Prevalence of crosstalks and interactions between parallel pathways renders any analysis probing the process of fate transition of hESCs elusive. This work presents an important step in the evaluation of network level interactions between signaling molecules controlling endoderm lineage specification from hESCs using a statistical network identification algorithm. Network analysis was performed on detailed signaling dynamics of key molecules from TGF-β/SMAD, PI3K/AKT and MAPK/ERK pathways under two common endoderm induction conditions. The results show the existence of significant crosstalk interactions during endoderm signaling and they identify differences in network connectivity between the induction conditions in the early and late phases of signaling dynamics. Predicted networks elucidate the significant effect of modulation of AKT mediated crosstalk leading to the success of PI3K inhibition in inducing efficient endoderm from hESCs in combination with TGF-β/SMAD signaling. View Full-TextKeywords:
dynamic bayesian networks; endoderm; human embryonic stem cells; network inference; signaling crosstalks
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Mathew, S.; Sundararaj, S.; Banerjee, I. Network Analysis Identifies Crosstalk Interactions Governing TGF-β Signaling Dynamics during Endoderm Differentiation of Human Embryonic Stem Cells. Processes 2015, 3, 286-308.
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