Network Analysis Identifies Crosstalk Interactions Governing TGF-β Signaling Dynamics during Endoderm Differentiation of Human Embryonic Stem Cells

Processes

Shibin Mathew¹  Sankaramanivel Sundararaj¹  Ipsita Banerjee¹ 

[1] Department of Chemical and Petroleum Engineering, University of Pittsburgh, Pittsburgh, PA 15261, USA; E-Mails:

关键词: dynamic bayesian networks;    endoderm;    human embryonic stem cells;    network inference;    signaling crosstalks;   

DOI  :  10.3390/pr3020286

来源: mdpi

【 摘 要 】

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.

【 授权许可】

CC BY   
© 2015 by the authors; licensee MDPI, Basel, Switzerland.