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胚胎脑源性神经干细胞暴露于酒精后的全基因组转录组景观，在 BL6 和 CD1 小鼠中进行了菌株特异性交叉检查。

Genome-Wide Transcriptome Landscape of Embryonic Brain-Derived Neural Stem Cells Exposed to Alcohol with Strain-Specific Cross-Examination in BL6 and CD1 Mice.

机构信息

Department of Biochemistry and Medical Genetics, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, Canada.

Research Institute of Oncology and Hematology, CancerCare Manitoba, Winnipeg, Canada.

出版信息

Sci Rep. 2019 Jan 18;9(1):206. doi: 10.1038/s41598-018-36059-y.

DOI:10.1038/s41598-018-36059-y
PMID:30659253
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6338767/
Abstract

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.

摘要

我们之前报道了乙醇对脑源性神经干细胞（NSC）全基因组 DNA 甲基化的去调控作用。在这里，我们对不同乙醇暴露模式下分化的 NSC 进行了全基因组 RNA-seq 分析。RNA-seq 结果显示，乙醇暴露和戒断会引起明显不同的基因表达模式和经典途径。短期乙醇暴露会导致突触途径异常上调，而持续的乙醇处理则会深刻影响脑细胞的形态。乙醇戒断恢复了分化 NSC 的基因表达谱，但未能挽救表观遗传因子的表达受损。IPA 分析预测，乙醇可能通过 GABA 受体信号通路影响突触功能，并影响神经系统和大脑形态。我们确定了 Sptbn2、Dcc 和 Scn3a 作为候选基因，IPA 分析预测这些基因可能将酒精诱导的神经元形态与大脑结构异常联系起来。对来自两种不同小鼠品系（BL6 和 CD1）的分化 NSC 中的 Scn3a 和 As3mt 进行交叉检查，结果显示分别呈诱导和减少的一致模式。总的来说，我们的研究确定了可能导致酒精介导的细胞和大脑结构畸形的遗传网络，为我们了解酒精对中枢神经系统的损伤提供了新的认识，为更好地理解 FASD 发病机制铺平了道路。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/539c/6338767/459a01fbe022/41598_2018_36059_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/539c/6338767/d5f3b587e31e/41598_2018_36059_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/539c/6338767/aed76aee475c/41598_2018_36059_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/539c/6338767/9ca3ba62e1c8/41598_2018_36059_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/539c/6338767/2137719432ea/41598_2018_36059_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/539c/6338767/6cf849343ebe/41598_2018_36059_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/539c/6338767/95896ca0c070/41598_2018_36059_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/539c/6338767/4e27f6a51556/41598_2018_36059_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/539c/6338767/459a01fbe022/41598_2018_36059_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/539c/6338767/d5f3b587e31e/41598_2018_36059_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/539c/6338767/aed76aee475c/41598_2018_36059_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/539c/6338767/9ca3ba62e1c8/41598_2018_36059_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/539c/6338767/2137719432ea/41598_2018_36059_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/539c/6338767/6cf849343ebe/41598_2018_36059_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/539c/6338767/95896ca0c070/41598_2018_36059_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/539c/6338767/4e27f6a51556/41598_2018_36059_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/539c/6338767/459a01fbe022/41598_2018_36059_Fig8_HTML.jpg

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