Transcriptomic analyses of gastrulation-stage mouse embryos with differential susceptibility to alcohol.
Transcriptomic analyses of gastrulation-stage mouse embryos with differential susceptibility to alcohol.
复制标题
对酒精敏感性差异的胃组小鼠胚胎的转录组分析。
DOI：
10.1242/dmm.049012
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发表时间：
2021-06-01
影响因子：
4.3
通讯作者：
Parnell SE
中科院分区：
文献类型：
--
作者：
Boschen KE;Ptacek TS;Berginski ME;Simon JM;Parnell SE
遗传是胎儿酒精谱系障碍（FASDs）患者和动物模型中酒精敏感性差异的一个已知因素。我们的研究分析了两种常用的基因相似的小鼠亚系C57BL/6J （6J）和C57BL/6NHsd （6N）在酒精敏感性不同的原肠胚期胚胎中的基因表达。首先，我们在原肠胚形成的三个精细分解的时间点建立了正常的基因表达模式，并开发了一个基于网络的互动工具。不同菌株的基线转录差异与免疫信号有关。其次，我们检查了每个菌株中受酒精影响的基因网络。与6N小鼠相比，酒精在6J小鼠中引起了更明显的转录效应，这与6J小鼠的易感性增加相匹配。6J菌株表现出细胞死亡、增殖、形态发生信号通路和颅面缺陷相关通路的失调，而6N菌株表现出缺氧和细胞代谢通路的富集。这些数据集提供了对小鼠原肠胚形成过程中不断变化的转录景观的深入了解，建立了一个有价值的资源，可以发现可能改变酒精易感性的候选基因，这些基因可以在人类中得到验证，并确定了新的酒精致病机制。编辑选择：原肠胚期小鼠胚胎的rna测序提供了正常小鼠发育过程中基因表达模式的信息，并证明了先前存在的遗传变异介导了产前酒精诱导的出生缺陷的风险。
Genetics are a known contributor to differences in alcohol sensitivity in humans with fetal alcohol spectrum disorders (FASDs) and in animal models. Our study profiled gene expression in gastrulation-stage embryos from two commonly used, genetically similar mouse substrains, C57BL/6J (6J) and C57BL/6NHsd (6N), that differ in alcohol sensitivity. First, we established normal gene expression patterns at three finely resolved time points during gastrulation and developed a web-based interactive tool. Baseline transcriptional differences across strains were associated with immune signaling. Second, we examined the gene networks impacted by alcohol in each strain. Alcohol caused a more pronounced transcriptional effect in the 6J versus 6N mice, matching the increased susceptibility of the 6J mice. The 6J strain exhibited dysregulation of pathways related to cell death, proliferation, morphogenic signaling and craniofacial defects, while the 6N strain showed enrichment of hypoxia and cellular metabolism pathways. These datasets provide insight into the changing transcriptional landscape across mouse gastrulation, establish a valuable resource that enables the discovery of candidate genes that may modify alcohol susceptibility that can be validated in humans, and identify novel pathogenic mechanisms of alcohol. . Editor's choice: RNA-sequencing in gastrulation-stage mouse embryos provides information about gene expression patterns during normal mouse development and evidence that pre-existing genetic variability mediates risk to prenatal alcohol-induced birth defects.
影响因子：
3.7
作者：
Örd T;Innos J;Lilleväli K;Tekko T;Sütt S;Örd D;Kõks S;Vasar E;Örd T
通讯作者：
Örd T