Institute of Systems Biomedicine, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, 100191, China.
Department of Pathology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, 100191, China.
Sci Rep. 2017 Jul 14;7(1):5435. doi: 10.1038/s41598-017-05882-0.
Postmortem mRNA degradation is considered to be the major concern in gene expression research utilizing human postmortem tissues. A key factor in this process is the postmortem interval (PMI), which is defined as the interval between death and sample collection. However, global patterns of postmortem mRNA degradation at individual gene levels across diverse human tissues remain largely unknown. In this study, we performed a systematic analysis of alteration of gene expression associated with PMI in human tissues. From the Genotype-Tissue Expression (GTEx) database, we evaluated gene expression levels of 2,016 high-quality postmortem samples from 316 donors of European descent, with PMI ranging from 1 to 27 hours. We found that PMI-related mRNA degradation is tissue-specific, gene-specific, and even genotype-dependent, thus drawing a more comprehensive picture of PMI-associated gene expression across diverse human tissues. Additionally, we also identified 266 differentially variable (DV) genes, such as DEFB4B and IFNG, whose expression is significantly dispersed between short PMI (S-PMI) and long PMI (L-PMI) groups. In summary, our analyses provide a comprehensive profile of PMI-associated gene expression, which will help interpret gene expression patterns in the evaluation of postmortem tissues.
死后 mRNA 降解被认为是利用人类死后组织进行基因表达研究的主要关注点。这个过程中的一个关键因素是死后间隔时间(PMI),它定义为死亡和样本采集之间的时间间隔。然而,在不同的人类组织中,个体基因水平上死后 mRNA 降解的全局模式在很大程度上仍然未知。在这项研究中,我们对与 PMI 相关的基因表达变化进行了系统分析。我们从基因型-组织表达(GTEx)数据库中评估了来自 316 名欧洲血统供体的 2016 个高质量死后样本的基因表达水平,PMI 范围为 1 至 27 小时。我们发现,PMI 相关的 mRNA 降解是组织特异性的、基因特异性的,甚至是基因型依赖性的,从而更全面地描绘了不同人类组织中与 PMI 相关的基因表达情况。此外,我们还鉴定了 266 个差异可变(DV)基因,如 DEFB4B 和 IFNG,它们的表达在短 PMI(S-PMI)和长 PMI(L-PMI)组之间存在显著差异。总之,我们的分析提供了与 PMI 相关的基因表达的综合概况,这将有助于解释死后组织评估中的基因表达模式。