Small RNA sequencing of postmortem human Brodmann Area 9 and postmortem human blood from Opioid Use Disorder Subjects and Controls in the University of Texas Health Science Center at Houston Brain Collection. Small RNA sequencing of postmortem human Brodmann Area 9 and postmortem human blood from Opioid Use Disorder Subjects and Controls in the University of Texas Health Science Center at Houston Brain Collection

This dataset includes samples in the UTHealth Brain Collection (UTHBC) from Grimm et al 2022 "MicroRNA-mRNA networks are dysregulated in opioid use disorder postmortem brain: further evidence for opioid-induced neurovascular alterations ", doi: 10.3389/fpsyt.2022.1025346. To understand mechanisms and identify potential targets for intervention in the current crisis of opioid use disorder (OUD), postmortem brains represent an under-utilized resource. To refine previously reported gene signatures of neurobiological alterations in OUD from the dorsolateral prefrontal cortex (Brodmann Area 9, BA9), we explored the role of microRNAs (miRNA) as powerful epigenetic regulators of gene function. Building on the growing appreciation that miRNAs can cross the blood-brain barrier, we carried out miRNA profiling in same-subject postmortem samples from BA9 and blood tissues. miRNA-mRNA network analysis showed that even though miRNAs identified in BA9 and blood were fairly distinct, their target genes and corresponding enriched pathways overlapped strongly. Among the dominant enriched biological processes were tissue development and morphogenesis, and MAPK signaling pathways. These findings point to robust, redundant, and systemic opioid-induced miRNA dysregulation with potential functional impact on transcriptomic changes. Further, using correlation network analysis we identified cell-type specific miRNA targets, specifically in astrocytes, neurons, and endothelial cells, associated with OUD transcriptomic dysregulation. Finally, leveraging a collection of control brain transcriptomes from the Genotype-Tissue Expression (GTEx) project, we identified correlation of OUD miRNA targets with TGF beta, hypoxia, angiogenesis, coagulation, immune system and inflammatory pathways. These findings support previous reports of neurovascular and immune system alterations as a consequence of opioid abuse and shed new light on miRNA network regulators of cellular response to opioid drugs. Overall design: Raw fastq for 39 brain Brodmann Area 9 samples (24 OUD and 15 controls) and 26 Blood Plasma Samples (18 opioid use disorder and 8 controls) from a subset of the same individuals in the UTHealth Brain Collection (UTHBC, RRID:SCR_022970). These individuals are a subset of those for which total RNA seq was performed in the GEO dataset GSE182321, found at https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE182321.

本数据集包含来自Grimm等人2022年发表的《阿片类药物使用障碍死后大脑中microRNA-mRNA网络失调：阿片类药物诱导神经血管改变的进一步证据》（DOI: 10.3389/fpsyt.2022.1025346）的UTHealth大脑采集库（UTHealth Brain Collection, UTHBC）中的样本。为解析阿片类药物使用障碍（opioid use disorder, OUD）当前危机中的发病机制并鉴定潜在干预靶点，死后大脑样本属于未被充分利用的研究资源。为优化此前报道的背外侧前额叶皮层Brodmann分区9区（Brodmann Area 9, BA9）中OUD相关神经生物学改变的基因特征，我们探究了microRNA（miRNA）作为基因功能强效表观遗传调控因子的作用。
鉴于学界对miRNA可跨越血脑屏障的认知日益加深，我们对来自同一受试者的BA9脑组织及血液组织的死后样本开展了miRNA表达谱分析。miRNA-mRNA网络分析显示，尽管BA9与血液中鉴定出的miRNA存在显著差异，但其靶基因及富集通路却高度重合。核心富集的生物学过程包括组织发育与形态发生，以及丝裂原活化蛋白激酶（mitogen-activated protein kinase, MAPK）信号通路。上述结果表明，阿片类药物诱导的miRNA失调具有广泛、冗余且系统性的特征，可对转录组变化产生潜在功能影响。
进一步通过相关网络分析，我们鉴定出与OUD转录组失调相关的细胞类型特异性miRNA靶标，具体涉及星形胶质细胞、神经元及内皮细胞。最后，依托基因型-组织表达（Genotype-Tissue Expression, GTEx）项目的对照脑转录组数据集，我们发现OUD的miRNA靶标与转化生长因子β（TGF beta）、缺氧、血管生成、凝血、免疫系统及炎症通路存在显著关联。本研究结果佐证了此前关于阿片类药物滥用可引发神经血管与免疫系统改变的报道，并为阿片类药物诱导的细胞应答miRNA网络调控因子提供了新见解。
总体设计：本数据集包含UTHealth大脑采集库（UTHBC, RRID:SCR_022970）中部分受试者的39例BA9脑组织样本（24例OUD患者、15例健康对照）及26例血浆样本（18例OUD患者、8例健康对照）的原始fastq数据。该队列的总RNA测序数据已收录于GEO数据集GSE182321，详情可访问链接：https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE182321。