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转录组学分析揭示精神分裂症患者外周血单个核细胞和脑组织中的共同通路。

Transcriptomics Analysis Reveals Shared Pathways in Peripheral Blood Mononuclear Cells and Brain Tissues of Patients With Schizophrenia.

作者信息

Song Xuemian, Liu Yiyun, Pu Juncai, Gui Siwen, Zhong Xiaogang, Chen Xiaopeng, Chen Weiyi, Chen Xiang, Chen Yue, Wang Haiyang, Cheng Ke, Zhao Libo, Xie Peng

机构信息

NHC Key Laboratory of Diagnosis and Treatment on Brain Functional Diseases, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.

State Key Laboratory of Ultrasound in Medicine and Engineering, Chongqing Medical University, Chongqing, China.

出版信息

Front Psychiatry. 2021 Sep 22;12:716722. doi: 10.3389/fpsyt.2021.716722. eCollection 2021.

DOI:10.3389/fpsyt.2021.716722
PMID:34630179
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8492981/
Abstract

Schizophrenia is a serious mental disorder with complicated biological mechanisms. Few studies explore the transcriptional features that are shared in brain tissue and peripheral blood. In the present study, we aimed to explore the biological pathways with similar expression patterns in both peripheral blood mononuclear cells (PBMCs) and brain tissues. The present study used transcriptomics technology to detect mRNA expression of PBMCs of 10 drug-naïve patients with schizophrenia and 20 healthy controls. Transcriptome data sets of brain tissue of patients with schizophrenia downloaded from public databases were also analyzed in our study. The biological pathways with similar expression patterns in the PBMCs and brain tissues were uncovered by differential expression analysis, weighted gene co-expression network analysis (WGCNA), and pathway analysis. Finally, the expression levels of differential expressed genes (DEGs) were validated by real-time fluorescence quantitative polymerase chain reaction (qPCR) in another 12 drug-naïve patients with schizophrenia and 12 healthy controls. We identified 542 DEGs, 51 DEGs, 732 DEGs, and 104 DEGs in PBMCs, dorsolateral prefrontal cortex, anterior cingulate gyrus, and nucleus accumbent, respectively. Five DEG clusters were recognized as having similar gene expression patterns in PBMCs and brain tissues by WGCNA. The pathway analysis illustrates that these DEG clusters are mainly enriched in several biological pathways that are related to phospholipid metabolism, ribosome signal transduction, and mitochondrial oxidative phosphorylation. The differential significance of , and were confirmed by qPCR. This study finds that the pathways associated with phospholipid metabolism, ribosome signal transduction, and energy metabolism have similar expression patterns in PBMCs and brain tissues of patients with schizophrenia. Our results supply a novel insight for revealing the pathogenesis of schizophrenia and might offer a new approach to explore potential biological markers of peripheral blood in schizophrenia.

摘要

精神分裂症是一种生物机制复杂的严重精神障碍。很少有研究探索脑组织和外周血中共享的转录特征。在本研究中,我们旨在探索外周血单个核细胞(PBMCs)和脑组织中具有相似表达模式的生物途径。本研究使用转录组学技术检测了10例未用药的精神分裂症患者和20例健康对照者的PBMCs的mRNA表达。我们的研究还分析了从公共数据库下载的精神分裂症患者脑组织的转录组数据集。通过差异表达分析、加权基因共表达网络分析(WGCNA)和途径分析,揭示了PBMCs和脑组织中具有相似表达模式的生物途径。最后,通过实时荧光定量聚合酶链反应(qPCR)在另外12例未用药的精神分裂症患者和12例健康对照者中验证了差异表达基因(DEGs)的表达水平。我们分别在PBMCs、背外侧前额叶皮层、前扣带回和伏隔核中鉴定出542个DEGs、51个DEGs、732个DEGs和104个DEGs。通过WGCNA识别出五个DEG簇在PBMCs和脑组织中具有相似的基因表达模式。途径分析表明,这些DEG簇主要富集于与磷脂代谢、核糖体信号转导和线粒体氧化磷酸化相关的几种生物途径中。qPCR证实了、和的差异显著性。本研究发现,与磷脂代谢、核糖体信号转导和能量代谢相关的途径在精神分裂症患者的PBMCs和脑组织中具有相似的表达模式。我们的结果为揭示精神分裂症的发病机制提供了新的见解,并可能为探索精神分裂症外周血潜在生物标志物提供新的方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ffc1/8492981/9f083469a152/fpsyt-12-716722-g0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ffc1/8492981/4c920ac1a93f/fpsyt-12-716722-g0001.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ffc1/8492981/9f083469a152/fpsyt-12-716722-g0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ffc1/8492981/4c920ac1a93f/fpsyt-12-716722-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ffc1/8492981/511d194b2032/fpsyt-12-716722-g0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ffc1/8492981/787d3c49de93/fpsyt-12-716722-g0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ffc1/8492981/a3b6c9f46bd8/fpsyt-12-716722-g0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ffc1/8492981/9f083469a152/fpsyt-12-716722-g0005.jpg

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