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Transcriptomic changes resulting from STK32B overexpression identifies pathways potentially relevant to essential tremor

ABSTRACT: We report RNA sequencing of overexpressed STK32B in DAOY cells compared to matched controls, with 200M reads per sample. We identified approximately 4000 differentially expressed genes and potential pathways relevant to essential tremor.

ORGANISM(S): Homo sapiens

PROVIDER: GSE150393 | GEO | 2020/05/13

REPOSITORIES: GEO

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Transcriptomic changes resulting from STK32B overexpression identifies pathways potentially relevant to essential tremor

Project description:Transcriptomic changes resulting from STK32B overexpression identifies pathways potentially relevant to essential tremor

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Transcriptomic Changes Resulting From <i>STK32B</i> Overexpression Identify Pathways Potentially Relevant to Essential Tremor.

Project description:Objective: Essential tremor (ET) is a common movement disorder that has a high heritability. A number of genetic studies have associated different genes and loci with ET, but few have investigated the biology of any of these genes. STK32B was significantly associated with ET in a large genome-wide association study (GWAS) and was found to be overexpressed in ET cerebellar tissue. The objective of this study is to determine the effects of overexpressed STK32B in cerebellar DAOY cells. Methods: Here, we overexpressed STK32B RNA in human cerebellar DAOY cells and used an RNA-Seq approach to identify differentially expressed genes (DEGs) by comparing the transcriptome profile of these cells to one of the control DAOY cells. Results: Pathway and gene ontology enrichment identified axon guidance, olfactory signaling, and calcium-voltage channels as significant. Additionally, we show that overexpressing STK32B affects transcript levels of previously implicated ET genes such as FUS. Conclusion: Our results investigate the effects of overexpressed STK32B and suggest that it may be involved in relevant ET pathways and genes.

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Transcriptomic effects of propranolol and primidone converge on molecular pathways relevant to essential tremor.

Project description:Essential tremor (ET) is one of the most common movement disorders, affecting nearly 5% of individuals over 65 years old. Despite this, few genetic risk loci for ET have been identified. Recent advances in pharmacogenomics have previously been useful to identify disease related molecular targets. Notably, gene expression has proven to be quite successful for the inference of drug response in cell models. We sought to leverage this approach in the context of ET where many patients are responsive to two drugs: propranolol and primidone. In this study, cerebellar DAOY and neural progenitor cells were treated for 5 days with clinical concentrations of propranolol and primidone, after which RNA-sequencing was used to identify convergent differentially expressed genes across treatments. Propranolol was found to affect the expression of genes previously associated with ET and other movement disorders such as TRAPPC11. Pathway enrichment analysis of these convergent drug-targeted genes identified multiple terms related to calcium signaling, endosomal sorting, axon guidance, and neuronal morphology. Furthermore, genes targeted by ET drugs were enriched within cell types having high expression of ET-related genes in both cortical and cerebellar tissues. Altogether, our results highlight potential cellular and molecular mechanisms associated with tremor reduction and identify relevant genetic biomarkers for drug-responsiveness in ET.

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