Next Article in Journal
A Chemical Engineering Perspective on the Origins of Life
Next Article in Special Issue
Special Issue on “Modeling and Analysis of Signal Transduction Networks” in the Journal Processes
Previous Article in Journal
A Novel ARX-Based Approach for the Steady-State Identification Analysis of Industrial Depropanizer Column Datasets
Previous Article in Special Issue
A Quantitative Systems Pharmacology Perspective on Cancer Immunology
Article Menu

Export Article

Open AccessArticle
Processes 2015, 3(2), 286-308; doi:10.3390/pr3020286

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
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)
View Full-Text   |   Download PDF [1413 KB, uploaded 4 May 2015]   |  

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-Text
Keywords: dynamic bayesian networks; endoderm; human embryonic stem cells; network inference; signaling crosstalks dynamic bayesian networks; endoderm; human embryonic stem cells; network inference; signaling crosstalks
Figures

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

Supplementary material

Scifeed alert for new publications

Never miss any articles matching your research from any publisher
  • Get alerts for new papers matching your research
  • Find out the new papers from selected authors
  • Updated daily for 49'000+ journals and 6000+ publishers
  • Define your Scifeed now

SciFeed Share & Cite This Article

MDPI and ACS Style

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.

Show more citation formats Show less citations formats

Related Articles

Article Metrics

Article Access Statistics

1

Comments

[Return to top]
Processes EISSN 2227-9717 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top