title: BDNF and the maturation of posttranscriptional regulatory networks in human SH-SY5Y neuroblast differentiation.
abstract: The SH-SY5Y culture system is a convenient neuronal model with the potential to elaborate human/primate-specific transcription networks and pathways related to human cognitive disorders. While this system allows for the exploration of specialized features in the human genome, there is still significant debate about how this model should be implemented, and its appropriateness for answering complex functional questions related to human neural architecture. In view of these questions we sought to characterize the posttranscriptional regulatory structure of the two-stage ATRA differentiation, BDNF maturation protocol proposed by Encinas et al. (2000) using integrative whole-genome gene and microRNA (miRNA) expression analysis. We report that ATRA-BDNF induced significant increases in expression of key synaptic genes, brain-specific miRNA and miRNA biogenesis machinery, and in AChE activity, compared with ATRA alone. Functional annotation clustering associated BDNF more significantly with neuronal terms, and with synaptic terms not found in ATRA-only clusters. While our results support use of SH-SY5Y as a neuronal model, we advocate considered selection of the differentiation agent/s relative to the system being modeled.
authors.affiliation: The Centre for Translational Neuroscience and Mental Health, School of Biomedical Sciences and Pharmacy, University of Newcastle Callaghan, NSW, Australia ; Schizophrenia Research Institute Sydney, NSW, Australia.
authors.forename: Belinda J
authors.initials: BJ
authors.lastname: Goldie
authors.affiliation: The Centre for Translational Neuroscience and Mental Health, School of Biomedical Sciences and Pharmacy, University of Newcastle Callaghan, NSW, Australia.
authors.forename: Michelle M
authors.initials: MM
authors.lastname: Barnett
authors.affiliation: The Centre for Translational Neuroscience and Mental Health, School of Biomedical Sciences and Pharmacy, University of Newcastle Callaghan, NSW, Australia ; Schizophrenia Research Institute Sydney, NSW, Australia.
authors.forename: Murray J
authors.initials: MJ
authors.lastname: Cairns
keywords: MicroRNAs; SH-SY5Y cells; cell culture techniques; gene expression profiling; neuronal differentiation