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

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.

journal_name

Cell Rep

journal_title

Cell reports

authors

Avey D,Sankararaman S,Yim AKY,Barve R,Milbrandt J,Mitra RD

doi

10.1016/j.celrep.2018.08.080

subject

Has Abstract

pub_date

2018-09-25 00:00:00

pages

3619-3629.e4

issue

13

issn

2211-1247

pii

S2211-1247(18)31384-6

journal_volume

24

pub_type

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