title: Chemogenomic analysis of neuronal differentiation with pathway changes in PC12 cells.
abstract: The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway database creates networks from interrelations between molecular biology and underlying chemical elements. This allows for analysis of biologic networks, genomic information, and higher-order functional information at a system level. Through high throughput experiments and system biology analysis, we investigated the genes and pathways associated with NGF induced neuronal differentiation. We performed microarray experiments and used the KEGG database, system biology analysis, and annotation of pathway functions to study NGF-induced differentiation in PC12 cells. We identified 2020 NGF-induced genes with altered expressions over time. Cross-matching with the KEGG database revealed 830 genes; among which, 395 altered genes were found to have a 2-fold increase in gene expression over a two-hour period. We then identified 191 associated biologic pathways in the KEGG database; the top 15 pathways showed correlation with neural differentiation. These included the neurotrophin pathways, mitogen-activated protein kinase (MAPK) pathways, genes associated with axonal guidance and the Wnt pathways. The activation of these pathways synchronized with nerve growth factor (NGF)-induced differentiation in PC12 cells. In summary, we have established a model system that allows one to systematically characterize the functional pathway changes in a group of neuronal population after an external stimulus.
authors.affiliation: Graduate Institute of Systems Biology and Bioinformatics, National Central University, Chungli, Taiwan, Republic of China. qdling@hotmail.com and Taipei Medical University Municipal Wan-Fang Hospital, Taipei, Taiwan, Republic of China.
authors.forename: Jack Yu-Shih
authors.initials: JY
authors.lastname: Lin
authors.affiliation: Taipei Medical University Municipal Wan-Fang Hospital, Taipei, Taiwan, Republic of China.
authors.forename: Chien Liang
authors.initials: CL
authors.lastname: Wu
authors.affiliation: Graduate Institute of Systems Biology and Bioinformatics, National Central University, Chungli, Taiwan, Republic of China. qdling@hotmail.com.
authors.forename: Chia Nan
authors.initials: CN
authors.lastname: Liao
authors.affiliation: Department of Chemical & Materials Engineering, National Central University, Chungli, Taiwan, Republic of China and Department of Botany and Microbiology, King Saud University, Riyadh, 11451, Saudi Arabia.
authors.forename: Akon
authors.initials: A
authors.lastname: Higuchi
authors.affiliation: Graduate Institute of Systems Biology and Bioinformatics, National Central University, Chungli, Taiwan, Republic of China. qdling@hotmail.com and Cathay Medical Research Institute, Cathay General Hospital, No. 32, Ln 160, Jian-Cheng Road, Shi-Zhi, Taipei, Taiwan, Republic of China. manto0719@gmail.com.
authors.forename: Qing-Dong
authors.initials: QD
authors.lastname: Ling
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D016000:Cluster Analysis; D019295:Computational Biology / Q000379:methods; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects; D053263:Gene Regulatory Networks; D023281:Genomics / Q000379:methods; D020932:Nerve Growth Factor / Q000494:pharmacology; D009474:Neurons / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D016716:PC12 Cells; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects; D059467:Transcriptome
chemical_list: D020932:Nerve Growth Factor