Department of Genetics, Washington University, School of Medicine, St. Louis, MO 63110, USA; Center for Genome Sciences and Systems Biology, Washington University, School of Medicine, St. Louis, MO 63110, USA.
Center for Genome Sciences and Systems Biology, Washington University, School of Medicine, St. Louis, MO 63110, USA.
Cell Rep. 2018 Sep 25;24(13):3619-3629.e4. doi: 10.1016/j.celrep.2018.08.080.
Molecular and behavioral responses to opioids are thought to be primarily mediated by neurons, although there is accumulating evidence that other cell types play a prominent role in drug addiction. To investigate cell-type-specific opioid responses, we performed single-cell RNA sequencing (scRNA-seq) of the nucleus accumbens of mice following acute morphine treatment. Differential expression analysis uncovered unique morphine-dependent transcriptional responses by oligodendrocytes and astrocytes. We examined the expression of selected genes, including Cdkn1a and Sgk1, by FISH, confirming their induction by morphine in oligodendrocytes. Further analysis using RNA-seq of FACS-purified oligodendrocytes revealed a large cohort of morphine-regulated genes. The affected genes are enriched for roles in cellular pathways intimately linked to oligodendrocyte maturation and myelination, including the unfolded protein response. Altogether, our data illuminate the morphine-dependent transcriptional response by oligodendrocytes and offer mechanistic insights into myelination defects associated with opioid abuse.
分子和行为对阿片类药物的反应被认为主要是由神经元介导的，尽管越来越多的证据表明其他细胞类型在药物成瘾中起着突出的作用。为了研究细胞类型特异性阿片类药物反应，我们对急性吗啡处理后的小鼠伏隔核进行了单细胞 RNA 测序 (scRNA-seq)。差异表达分析揭示了少突胶质细胞和星形胶质细胞独特的依赖吗啡的转录反应。我们通过 FISH 检查了选定基因（包括 Cdkn1a 和 Sgk1）的表达，证实了它们在少突胶质细胞中被吗啡诱导。使用 FACS 纯化的少突胶质细胞进行 RNA-seq 的进一步分析揭示了一大群受吗啡调控的基因。受影响的基因富集了与少突胶质细胞成熟和髓鞘形成密切相关的细胞途径的作用，包括未折叠蛋白反应。总的来说，我们的数据阐明了少突胶质细胞中依赖吗啡的转录反应，并为与阿片类药物滥用相关的髓鞘缺陷提供了机制上的见解。
