Jul 8, 2016

Schizophrenia hiPSC neurons display expression changes that are enriched for disease risk variants and a blunted activity-dependent response

BioRxiv : the Preprint Server for Biology
Panos RoussosKristen J Brennand

Abstract

IMPORTANCE: Schizophrenia (SCZ) is a common illness with complex genetic architecture where both common genetic variation and rare mutations have been implicated. SCZ candidate genes participate in common molecular pathways that are regulated by activity-dependent changes in neurons, including the signaling network that modulates synaptic strength and the network of genes that are targets of fragile X mental retardation protein. One important next step is to further our understanding on the role of activity-dependent changes of genes expression in the etiopathogenesis of SCZ. OBJECTIVE: To examine whether neuronal activity-dependent changes of gene expression is dysregulated in SCZ. DESIGN, SETTING, AND PARTICIPANTS: Neurons differentiated from human induced pluripotent stem cells (hiPSCs) derived from 4 cases with SCZ and 4 unaffected controls were depolarized using potassium chloride. RNA was extracted followed by genome-wide profiling of the transcriptome. MAIN OUTCOMES AND MEASURES: We performed differential expression analysis and gene co-expression analysis to identify activity-dependent or disease-specific changes of the transcriptome. Further, we used gene set analyses to identify co-expressed modules that are enriched ...Continue Reading

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Mentioned in this Paper

Genome-Wide Association Study
Biochemical Pathway
Fragile X Syndrome
Pluripotent Stem Cells
Genes
Schizophrenia
Transcription, Genetic
Neurons
Candidate Disease Gene
Human Induced Pluripotent Stem Cells

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