PDF(Pubmed)
Abstract：
Elucidating mechanisms by which early-life adversity (ELA) contributes to increased disease risk is important for mitigating adverse health outcomes. Prior work has found differences in immune cell gene expression related to inflammation and mitochondrial activity. Using a within-person between-group experimental design, we investigated differences in gene expression clusters across acute psychosocial stress and no-stress conditions. Participants were young adults (N = 29, aged 18 - 25 years, 62 % female, 47 % with a history of ELA). Gene expression was assessed in peripheral blood mononuclear cells collected at 8 blood draws spanning two 5-hour sessions (stress vs. no-stress) separated by a week, 4 across each session (number of observations = 221). We applied two unsupervised gene clustering methods - latent profile analysis (LPA) and weighted gene co-expression analysis (WGCNA) - to cluster genes with similar expression patterns across participants. LPA identified 11 clusters, 7 of which were significantly associated with ELA-status. WGCNA identified 5 clusters, 3 of which were significantly associated with ELA-status. LPA- and WGCNA-identified clusters were correlated, and all clusters were highly preserved across sessions and time. There was no significant effect of acute stress on cluster gene expression, but there was a significant effect of time, and significant differences by ELA-status. ELA-associated clusters related to RNA splicing/processing, inflammation, leukocyte differentiation and division, and mitochondrial activity were differentially expressed across time: ELA-exposed individuals showed decreased expression of these clusters at 90-minutes while controls showed increased expression. Our findings replicate previous work in this area and highlight additional mechanisms by which ELA may contribute to disease risk.
摘要：
阐明生命早期逆境（ELA）导致疾病风险增加的机制对于减轻不良健康结果很重要。先前的工作已经发现与炎症和线粒体活性相关的免疫细胞基因表达的差异。使用人体内组间实验设计，我们调查了急性心理社会应激和无应激条件下基因表达簇的差异.参与者是年轻人(N=29，年龄18-25岁，62%女性,47%有ELA病史)。在两次5小时的8次抽血时收集的外周血单核细胞中评估了基因表达（压力与无压力)相隔一周，4在每个会话中(观察次数=221)。我们应用了两种无监督的基因聚类方法-潜在谱分析（LPA）和加权基因共表达分析（WGCNA）-对参与者之间具有相似表达模式的基因进行聚类。LPA确定了11个集群，其中7例与ELA状态显著相关。WGCNA确定了5个集群，其中3例与ELA状态显著相关。LPA和WGCNA识别的簇是相关的，所有的集群都在不同的会话和时间高度保留。急性应激对簇基因表达无显著影响，但是时间的影响很大，和ELA状态的显著差异。与RNA剪接/加工相关的ELA相关簇，炎症,白细胞分化和分裂，线粒体活性随时间差异表达：暴露于ELA的个体在90分钟时显示这些簇的表达降低，而对照组显示表达增加。我们的发现重复了该领域的先前工作，并强调了ELA可能导致疾病风险的其他机制。
