Miyahara Kazusa, Hino Mizuki, Yu Zhiqian, Ono Chiaki, Nagaoka Atsuko, Hatano Masataka, Shishido Risa, Yabe Hirooki, Tomita Hiroaki, Kunii Yasuto
Department of Disaster Psychiatry, International Research Institute of Disaster Science, Tohoku University, Sendai, Japan.
Department of Neuropsychiatry, School of Medicine, Fukushima Medical University, Fukushima, Japan.
Front Psychiatry. 2023 Jul 14;14:1156524. doi: 10.3389/fpsyt.2023.1156524. eCollection 2023.
Evaluating and controlling confounders are necessary when investigating molecular pathogenesis using human postmortem brain tissue. Particularly, tissue pH and RNA integrity number (RIN) are valuable indicators for controlling confounders. However, the influences of these indicators on the expression of each gene in postmortem brain have not been fully investigated. Therefore, we aimed to assess these effects on gene expressions of human brain samples.
We isolated total RNA from occipital lobes of 13 patients with schizophrenia and measured the RIN and tissue pH. Gene expression was analyzed and gene sets affected by tissue pH and RIN were identified. Moreover, we examined the functions of these genes by enrichment analysis and upstream regulator analysis.
We identified 2,043 genes (24.7%) whose expressions were highly correlated with pH; 3,004 genes (36.3%) whose expressions were highly correlated with RIN; and 1,293 genes (15.6%) whose expressions were highly correlated with both pH and RIN. Genes commonly affected by tissue pH and RIN were highly associated with energy production and the immune system. In addition, genes uniquely affected by tissue pH were highly associated with the cell cycle, whereas those uniquely affected by RIN were highly associated with RNA processing.
The current study elucidated the influence of pH and RIN on gene expression profiling and identified gene sets whose expressions were affected by tissue pH or RIN. These findings would be helpful in the control of confounders for future postmortem brain studies.
在使用人类死后脑组织研究分子发病机制时，评估和控制混杂因素是必要的。特别是，组织pH值和RNA完整性数值（RIN）是控制混杂因素的重要指标。然而，这些指标对死后大脑中每个基因表达的影响尚未得到充分研究。因此，我们旨在评估这些因素对人类脑样本基因表达的影响。
我们从13例精神分裂症患者的枕叶中分离出总RNA，并测量了RIN和组织pH值。分析了基因表达情况，确定了受组织pH值和RIN影响的基因集。此外，我们通过富集分析和上游调节因子分析研究了这些基因的功能。
我们鉴定出2043个基因（24.7%），其表达与pH值高度相关；3004个基因（36.3%），其表达与RIN高度相关；以及1293个基因（15.6%），其表达与pH值和RIN均高度相关。受组织pH值和RIN共同影响的基因与能量产生和免疫系统高度相关。此外，仅受组织pH值影响的基因与细胞周期高度相关，而仅受RIN影响的基因与RNA加工高度相关。
本研究阐明了pH值和RIN对基因表达谱的影响，并确定了其表达受组织pH值或RIN影响的基因集。这些发现将有助于未来死后大脑研究中混杂因素的控制。
