Dataset Information

Genome-wide profiling of differentially spliced mRNAs in human fetal cortical tissue exposed to alcohol.

ABSTRACT: Excessive alcohol consumption results in significant changes in gene expression and isoforms due to altered mRNA splicing. As such, an intriguing possibility is that disturbances in alternative splicing are involved in key pathological pathways triggered by alcohol exposure. However, no resources have been available to systematically analyze this possibility at a genome-wide scale. Here, we performed RNA sequencing of human fetal cortical slices that were obtained at the late first trimester and exposed to ethanol or control medium. We report 382 events that were identified as changes affecting the ratio of splicing isoforms in the ethanol-exposed fetal human cortex. Additionally, previously unreported novel isoforms of several genes were also identified. These results provide a broad perspective on the post-transcriptional regulatory network underlying ethanol-induced pathogenesis in the developing human cortex.

SUBMITTER: Kawasawa YI

PROVIDER: S-EPMC7336896 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Genome-wide profiling of differentially spliced mRNAs in human fetal cortical tissue exposed to alcohol.

Kawasawa Yuka Imamura YI Mohammad Shahid S Son Alexander I AI Morizono Hiroki H Basha Aiesha A Salzberg Anna C AC Torii Masaaki M Hashimoto-Torii Kazue K

Alcohol (Fayetteville, N.Y.) 20170504

Excessive alcohol consumption results in significant changes in gene expression and isoforms due to altered mRNA splicing. As such, an intriguing possibility is that disturbances in alternative splicing are involved in key pathological pathways triggered by alcohol exposure. However, no resources have been available to systematically analyze this possibility at a genome-wide scale. Here, we performed RNA sequencing of human fetal cortical slices that were obtained at the late first trimester and ...[more]

PMID: 28755746

Similar Datasets

Project description:BackgroundElectronic-cigarette (e-cig) usage, particularly in the youth population, is a growing concern. It is known that e-cig causes endothelial dysfunction, which is a risk factor for the development of cardiovascular diseases; however, the mechanisms involved remain unclear. We hypothesized that long noncoding RNAs (lncRNAs) may play a role in e-cig-induced endothelial dysfunction.MethodsHere, we identified lncRNAs that are dysregulated in human induced pluripotent stem cell-derived endothelial cells (iPSC-ECs) following 24 h of e-cig aerosol extract treatment via microarray analysis. We performed Gene Ontology and Kyoto Encyclopedia of Genes and Genome (KEGG) pathway analyses of the dysregulated mRNAs following e-cig exposure and constructed co-expression networks of the top 5 upregulated lncRNAs and the top 5 downregulated lncRNAs and the mRNAs that are correlated with them. Furthermore, the functional effects of knocking down lncRNA lung cancer-associated transcript 1 (LUCAT1) on EC phenotypes were determined as it was one of the significantly upregulated lncRNAs following e-cig exposure based on our profiling.Results183 lncRNAs and 132 mRNAs were found to be upregulated, whereas 297 lncRNAs and 413 mRNAs were found to be downregulated after e-cig exposure. We also observed that e-cig caused dysregulation of endothelial metabolism resulting in increased FAO activity, higher mitochondrial membrane potential, and decreased glucose uptake and glycolysis. These results suggest that e-cig alters EC metabolism by increasing FAO to compensate for energy deficiency in ECs. Finally, the knockdown of LUCAT1 prevented e-cig-induced EC dysfunction by maintaining vascular barrier, reducing reactive oxygen species level, and increasing migration capacity.ConclusionThis study identifies an expression profile of differentially expressed lncRNAs and several potential regulators and pathways in ECs exposed to e-cig, which provide insights into the regulation of lncRNAs and mRNAs and the role of lncRNA and mRNA networks in ECs associated e-cig exposure.

Dataset Information

Genome-wide profiling of differentially spliced mRNAs in human fetal cortical tissue exposed to alcohol.

Publications

Genome-wide profiling of differentially spliced mRNAs in human fetal cortical tissue exposed to alcohol.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets