Single-Cell RNA-Seq Uncovers a Robust Transcriptional Response to Morphine by Glia

Denis Avey, Sumithra Sankararaman, Aldrin K.Y. Yim, Ruteja Barve, Jeffrey Milbrandt, Robi D Mitra. Cell Reports, Volume 24, Issue 13, 25 September 2018, Pages 3619-3629.e4 Read More

Abstract

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. Avey et al. use single-cell RNA-seq to uncover cell-type-specific responses to morphine in the brains of mice, revealing a unique and robust response by oligodendrocytes, which they further validate by multiple approaches. These analyses offer insights into the molecular mechanisms underlying oligodendrocyte dysfunction in the context of opioid abuse. © 2018 The Authors

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Posted on October 4, 2018
Posted in: Axon Injury & Repair, Neurogenetics & Transcriptomics, Publications Authors: ,