Phenotypic Characterization of Retinoic Acid Differentiated SH-SY5Y Cells by Transcriptional Profiling
Open Access
- 28 May 2013
- journal article
- research article
- Published by Public Library of Science (PLoS) in PLOS ONE
- Vol. 8 (5), e63862
- https://doi.org/10.1371/journal.pone.0063862
Abstract
Multiple genetic and environmental factors play a role in the development and progression of Parkinson’s disease (PD). The main neuropathological hallmark of PD is the degeneration of dopaminergic (DAergic) neurons in the substantia nigra pars compacta. To study genetic and molecular contributors to the disease process, there is a great need for readily accessible cells with prominent DAergic features that can be used for reproducible in vitro cellular screening. Here, we investigated the molecular phenotype of retinoic acid (RA) differentiated SH-SY5Y cells using genome wide transcriptional profiling combined with gene ontology, transcription factor and molecular pathway analysis. We demonstrated that RA induces a general neuronal differentiation program in SH-SY5Y cells and that these cells develop a predominantly mature DAergic-like neurotransmitter phenotype. This phenotype is characterized by increased dopamine levels together with a substantial suppression of other neurotransmitter phenotypes, such as those for noradrenaline, acetylcholine, glutamate, serotonin and histamine. In addition, we show that RA differentiated SH-SY5Y cells express the dopamine and noradrenalin neurotransmitter transporters that are responsible for uptake of MPP(+), a well known DAergic cell toxicant. MPP(+) treatment alters mitochondrial activity according to its proposed cytotoxic effect in DAergic neurons. Taken together, RA differentiated SH-SY5Y cells have a DAergic-like phenotype, and provide a good cellular screening tool to find novel genes or compounds that affect cytotoxic processes that are associated with PD.Keywords
This publication has 68 references indexed in Scilit:
- A novel function of the proneural factor Ascl1 in progenitor proliferation identified by genome-wide characterization of its targetsGenes & Development, 2011
- Polyamine pathway contributes to the pathogenesis of Parkinson diseaseProceedings of the National Academy of Sciences of the United States of America, 2010
- Intensity-based analysis of dual-color gene expression data as an alternative to ratio-based analysis to enhance reproducibilityBMC Genomics, 2010
- Nrf2 promotes neuronal cell differentiationFree Radical Biology & Medicine, 2009
- Gene expression profiling of substantia nigra dopamine neurons: further insights into Parkinson's disease pathologyBrain, 2008
- A Transcriptome Database for Astrocytes, Neurons, and Oligodendrocytes: A New Resource for Understanding Brain Development and FunctionJournal of Neuroscience, 2008
- Axonal netrin-Gs transneuronally determine lamina-specific subdendritic segmentsProceedings of the National Academy of Sciences of the United States of America, 2007
- Linear Models and Empirical Bayes Methods for Assessing Differential Expression in Microarray ExperimentsStatistical Applications in Genetics and Molecular Biology, 2004
- Dependence on electron transport chain function and intracellular signaling of genomic responses in SH-SY5Y cells to the mitochondrial neurotoxin MPP+Experimental Neurology, 2003
- Gene Expression Omnibus: NCBI gene expression and hybridization array data repositoryNucleic Acids Research, 2002