title: Synergistic transcriptional and post-transcriptional regulation of ESC characteristics by core pluripotency transcription factors in protein-protein interaction networks.
abstract: The molecular mechanism that maintains the pluripotency of embryonic stem cells (ESCs) is not well understood but may be reflected in complex biological networks. However, there have been few studies on the effects of transcriptional and post-transcriptional regulation during the development of ESCs from the perspective of computational systems biology. In this study, we analyzed the topological properties of the "core" pluripotency transcription factors (TFs) OCT4, SOX2 and NANOG in protein-protein interaction networks (PPINs). Further, we identified synergistic interactions between these TFs and microRNAs (miRNAs) in PPINs during ESC development. Results show that there were significant differences in centrality characters between TF-targets and non-TF-targets in PPINs. We also found that there was consistent regulation of multiple "core" pluripotency TFs. Based on the analysis of shortest path length, we found that the module properties were not only within the targets regulated by common or multiple "core" pluripotency TFs but also between the groups of targets regulated by different TFs. Finally, we identified synergistic regulation of these TFs and miRNAs. In summary, the synergistic effects of "core" pluripotency TFs and miRNAs were analyzed using computational methods in both human and mouse PPINs.
authors.affiliation: College of Life Sciences, Northwest A&F University, Yangling, Shaanxi, China.
authors.forename: Leijie
authors.initials: L
authors.lastname: Li
authors.affiliation: College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, China; Department of Statistics, Rice University, Houston, TX, United States of America.
authors.forename: Liangcai
authors.initials: L
authors.lastname: Zhang
authors.affiliation: College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, China; Genome Analysis Laboratory, Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, Tianjin, China.
authors.forename: Guiyou
authors.initials: G
authors.lastname: Liu
authors.affiliation: College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, China; Department of Nutrition and Food Hygiene, School of Public Health, Harbin Medical University, Harbin, China.
authors.forename: Rennan
authors.initials: R
authors.lastname: Feng
authors.affiliation: College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, China.
authors.forename: Yongshuai
authors.initials: Y
authors.lastname: Jiang
authors.affiliation: College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Yang
authors.affiliation: Department of Biostatistics, School of Science, Anhui Agricultural University, Hefei, China.
authors.forename: Shihua
authors.initials: S
authors.lastname: Zhang
authors.affiliation: College of Life Sciences, Northwest A&F University, Yangling, Shaanxi, China.
authors.forename: Mingzhi
authors.initials: M
authors.lastname: Liao
authors.affiliation: College of Veterinary Medicine, Shaanxi Centre of Stem Cells Engineering & Technology, Northwest A&F University, Yangling, Shaanxi, China.
authors.forename: Jinlian
authors.initials: J
authors.lastname: Hua
mesh_terms: D000818:Animals; D053595:Embryonic Stem Cells / Q000378:metabolism*; D005786:Gene Expression Regulation; D053263:Gene Regulatory Networks; D018398:Homeodomain Proteins / Q000378:metabolism; D006801:Humans; D051379:Mice; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism; D000071317:Nanog Homeobox Protein; D050814:Octamer Transcription Factor-3 / Q000378:metabolism; D060066:Protein Interaction Maps; D055748:SOXB1 Transcription Factors / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism*; D015533:Transcriptional Activation
chemical_list: D018398:Homeodomain Proteins; D035683:MicroRNAs; C486780:NANOG protein, human; D000071317:Nanog Homeobox Protein; C475540:Nanog protein, mouse; D050814:Octamer Transcription Factor-3; D055748:SOXB1 Transcription Factors; D014157:Transcription Factors