Genome-Wide Transcriptome Landscape of Embryonic Brain-Derived Neural Stem Cells Exposed to Alcohol with Strain-Specific Cross-Examination in BL6 and CD1 Mice
| Autor: | Carl O. Olson, Robby M. Zachariah, Geoffrey G. Hicks, Wayne Xu, Romina D. Levy, Aaron MacAulay, James R. Davie, Kyle Curtis, Marjorie Buist, Shayan Amiri, Mojgan Rastegar, Vichithra R. B. Liyanage |
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| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
Male
0301 basic medicine Candidate gene lcsh:Medicine Mice Inbred Strains Biology Article Epigenesis Genetic Transcriptome Mice 03 medical and health sciences 0302 clinical medicine Neural Stem Cells Pregnancy Gene expression NAV1.3 Voltage-Gated Sodium Channel Animals Gene Regulatory Networks Epigenetics Ethanol metabolism lcsh:Science Neurons Multidisciplinary Ethanol Sequence Analysis RNA Gene Expression Profiling lcsh:R Brain Central Nervous System Depressants Cell Differentiation DNA Methylation Neural stem cell Hedgehog signaling pathway Substance Withdrawal Syndrome Cell biology Mice Inbred C57BL Alcoholism 030104 developmental biology Prenatal Exposure Delayed Effects DNA methylation Female lcsh:Q 030217 neurology & neurosurgery Genome-Wide Association Study |
| Zdroj: | Scientific Reports, Vol 9, Iss 1, Pp 1-17 (2019) Scientific Reports |
| ISSN: | 2045-2322 |
| Popis: | We have previously reported the deregulatory impact of ethanol on global DNA methylation of brain-derived neural stem cells (NSC). Here, we conducted a genome-wide RNA-seq analysis in differentiating NSC exposed to different modes of ethanol exposure. RNA-seq results showed distinct gene expression patterns and canonical pathways induced by ethanol exposure and withdrawal. Short-term ethanol exposure caused abnormal up-regulation of synaptic pathways, while continuous ethanol treatment profoundly affected brain cells’ morphology. Ethanol withdrawal restored the gene expression profile of differentiating NSC without rescuing impaired expression of epigenetics factors. Ingenuity Pathway Analysis (IPA) analysis predicated that ethanol may impact synaptic functions via GABA receptor signalling pathway and affects neural system and brain morphology. We identified Sptbn2, Dcc, and Scn3a as candidate genes which may link alcohol-induced neuronal morphology to brain structural abnormalities, predicted by IPA analysis. Cross-examination of Scn3a and As3mt in differentiated NSC from two different mouse strains (BL6 and CD1) showed a consistent pattern of induction and reduction, respectively. Collectively, our study identifies genetic networks, which may contribute to alcohol-mediated cellular and brain structural dysmorphology, contributing to our knowledge of alcohol-mediated damage to central nervous system, paving the path for better understanding of FASD pathobiology. |
| Databáze: | OpenAIRE |
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