High-throughput screening and classification of chemicals and their effects on neuronal gene expression using RASL-seq.

Autor: Simon JM; Department of Cell Biology and Physiology, UNC Neuroscience Center, The University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA.; Carolina Institute for Developmental Disabilities, The University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA.; Department of Genetics, The University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA.; Lineberger Comprehensive Cancer Center, The University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA., Paranjape SR; Department of Cell Biology and Physiology, UNC Neuroscience Center, The University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA., Wolter JM; Department of Cell Biology and Physiology, UNC Neuroscience Center, The University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA., Salazar G; Department of Cell Biology and Physiology, UNC Neuroscience Center, The University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA., Zylka MJ; Department of Cell Biology and Physiology, UNC Neuroscience Center, The University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA. zylka@med.unc.edu.; Carolina Institute for Developmental Disabilities, The University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA. zylka@med.unc.edu.
Jazyk: angličtina
Zdroj: Scientific reports [Sci Rep] 2019 Mar 14; Vol. 9 (1), pp. 4529. Date of Electronic Publication: 2019 Mar 14.
DOI: 10.1038/s41598-019-39016-5
Abstrakt: We previously used RNA-seq to identify chemicals whose effects on neuronal gene expression mimicked transcriptional signatures of autism, aging, and neurodegeneration. However, this approach was costly and time consuming, which limited our study to testing a single chemical concentration on mixed sex cortical neuron cultures. Here, we adapted a targeted transcriptomic method (RASL-seq, similar to TempO-seq) to interrogate changes in expression of a set of 56 signature genes in response to a library of 350 chemicals and chemical mixtures at four concentrations in male and female mouse neuronal cultures. This enabled us to replicate and expand our previous classifications, and show that transcriptional responses were largely equivalent between sexes. Overall, we found that RASL-seq can be used to accelerate the pace at which chemicals and mixtures that transcriptionally mimic autism and other neuropsychiatric diseases can be identified, and provides a cost-effective way to quantify gene expression with a panel of marker genes.
Databáze: MEDLINE
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