title: Identifying Tmem59 related gene regulatory network of mouse neural stem cell from a compendium of expression profiles.
abstract: BACKGROUND
  Neural stem cells offer potential treatment for neurodegenerative disorders, such like Alzheimer's disease (AD). While much progress has been made in understanding neural stem cell function, a precise description of the molecular mechanisms regulating neural stem cells is not yet established. This lack of knowledge is a major barrier holding back the discovery of therapeutic uses of neural stem cells. In this paper, the regulatory mechanism of mouse neural stem cell (NSC) differentiation by tmem59 is explored on the genome-level.
  
  
  RESULTS
  We identified regulators of tmem59 during the differentiation of mouse NSCs from a compendium of expression profiles. Based on the microarray experiment, we developed the parallelized SWNI algorithm to reconstruct gene regulatory networks of mouse neural stem cells. From the inferred tmem59 related gene network including 36 genes, pou6f1 was identified to regulate tmem59 significantly and might play an important role in the differentiation of NSCs in mouse brain. There are four pathways shown in the gene network, indicating that tmem59 locates in the downstream of the signalling pathway. The real-time RT-PCR results shown that the over-expression of pou6f1 could significantly up-regulate tmem59 expression in C17.2 NSC line. 16 out of 36 predicted genes in our constructed network have been reported to be AD-related, including Ace, aqp1, arrdc3, cd14, cd59a, cds1, cldn1, cox8b, defb11, folr1, gdi2, mmp3, mgp, myrip, Ripk4, rnd3, and sncg. The localization of tmem59 related genes and functional-related gene groups based on the Gene Ontology (GO) annotation was also identified.
  
  
  CONCLUSIONS
  Our findings suggest that the expression of tmem59 is an important factor contributing to AD. The parallelized SWNI algorithm increased the efficiency of network reconstruction significantly. This study enables us to highlight novel genes that may be involved in NSC differentiation and provides a shortcut to identifying genes for AD.
authors.affiliation: Laboratory of Molecular Neurobiology, Institute of Systems Biology, School of Life Sciences, Shanghai University, 99 Shangda Road, Shanghai 200433, China.
authors.forename: Luwen
authors.initials: L
authors.lastname: Zhang
authors.forename: Xiangchun
authors.initials: X
authors.lastname: Ju
authors.forename: Yumin
authors.initials: Y
authors.lastname: Cheng
authors.forename: Xiuyun
authors.initials: X
authors.lastname: Guo
authors.forename: Tieqiao
authors.initials: T
authors.lastname: Wen
mesh_terms: D000465:Algorithms; D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism*; D000704:Analysis of Variance; D000818:Animals; D002454:Cell Differentiation / Q000502:physiology*; D017931:DNA Primers / Q000235:genetics; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D053263:Gene Regulatory Networks / Q000502:physiology*; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D046228:Microarray Analysis; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D058953:Neural Stem Cells / Q000502:physiology*; D050809:POU Domain Factors / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D017931:DNA Primers; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D050809:POU Domain Factors; C489996:Pou6f1 protein, mouse; C000626540:Tmem59 protein, mouse