A systems biology approach to identify the signalling network regulated by Rho-GDI-γ during neural stem cell differentiation.
Understanding the molecular mechanism that underlies the differentiation of neural stem cells (NSCs) is vital to develop regenerative medicines for neurological disorders. In our previous work, Rho-GDI-γ was found to be able to prompt neuronal differentiation when it was down regulated. However, it is unclear how Rho-GDI-γ regulates this differentiation process. Therefore, a novel systems biology approach is presented here to identify putative signalling pathways regulated by Rho-GDI-γ during NSC differentiation, and these pathways can provide insights into the NSC differentiation mechanisms. In particular, our proposed approach combines the predictive power of computational biology and molecular experiments. With different biological experiments, the genes in the computationally identified signalling network were validated to be indeed regulated by Rho-GDI-γ during the differentiation of NSCs. In particular, one randomly selected pathway involving Vcp, Mapk8, Ywhae and Ywhah was experimentally verified to be regulated by Rho-GDI-γ. These promising results demonstrate the effectiveness of our proposed systems biology approach, indicating the potential predictive power of integrating computational and experimental approaches.
Institute of Systems Biology, Shanghai University, Shanghai 200444, China.
Jiao
J
Wang
Fuyan
F
Hu
Hua
H
Cheng
Xing-Ming
XM
Zhao
Tieqiao
T
Wen
D048948:14-3-3 Proteins / Q000235:genetics / Q000378:metabolism; D000251:Adenosine Triphosphatases / Q000235:genetics / Q000378:metabolism; D000818:Animals; D015153:Blotting, Western; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics; D002460:Cell Line; D019295:Computational Biology; D005455:Fluorescent Antibody Technique; D051379:Mice; D048055:Mitogen-Activated Protein Kinase 8 / Q000235:genetics / Q000378:metabolism; D058953:Neural Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D049490:Systems Biology / Q000379:methods*; D000074405:Valosin Containing Protein; D062950:rho Guanine Nucleotide Dissociation Inhibitor gamma / Q000494:pharmacology*
D048948:14-3-3 Proteins; D018797:Cell Cycle Proteins; C576823:Ywhae protein, mouse; D062950:rho Guanine Nucleotide Dissociation Inhibitor gamma; D048055:Mitogen-Activated Protein Kinase 8; D000251:Adenosine Triphosphatases; D000074405:Valosin Containing Protein; C000614179:Vcp protein, mouse