title: Differential variability and correlation of gene expression identifies key genes involved in neuronal differentiation.
abstract: BACKGROUND
  Understanding the dynamics of stem cell differentiation processes at the molecular level is a central challenge in developmental biology and regenerative medicine. Although the dynamic behaviors of differentiation regulators have been partially characterized, the architecture regulating the underlying molecular systems remains unclear.
  
  
  RESULTS
  System-level analysis of transcriptional data was performed to characterize the dynamics of molecular networks in neural differentiation of stem cells. Expression of a network module of genes tightly co-expressed in mouse embryonic stem (ES) cells fluctuated greatly among cell populations before differentiation, but became stable following neural differentiation. During the neural differentiation process, genes exhibiting both differential variance and differential correlation between undifferentiated and differentiating states were related to developmental functions such as body axis development, neuronal movement, and transcriptional regulation. Furthermore, these genes were genetically associated with neuronal differentiation, providing support for the idea they are not only differentiation markers but could also play important roles in neural differentiation. Comparisons with transcriptional data from human induced pluripotent stem (iPS) cells revealed that the system of genes dynamically regulated during neural differentiation is conserved between mouse and human.
  
  
  CONCLUSIONS
  The results of this study provide a systematic analytical framework for identifying key genes involved in neural differentiation by detecting their dynamical behaviors, as well as a basis for understanding the dynamic molecular mechanisms underlying the processes of neural differentiation.
authors.affiliation: Department of Biotechnology, Graduate School of Engineering, Nagoya University, Nagoya, Aichi, Japan. tat2uya@gmail.com.
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Ando
authors.affiliation: Department of Basic Medicinal Sciences, Graduate School of Pharmaceutical Sciences, Nagoya University, Nagoya, Aichi, Japan. kato-r@ps.nagoya-u.ac.jp.
authors.forename: Ryuji
authors.initials: R
authors.lastname: Kato
authors.affiliation: Department of Biotechnology, Graduate School of Engineering, Nagoya University, Nagoya, Aichi, Japan. honda@nubio.nagoya-u.ac.jp.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Honda
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000235:genetics*; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D053263:Gene Regulatory Networks; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000378:metabolism; D051379:Mice; D008957:Models, Genetic; D000066450:Mouse Embryonic Stem Cells; D009474:Neurons / Q000166:cytology* / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism; D049490:Systems Biology / Q000379:methods