Single-cell RNA-seq uncovers a robust transcriptional response to morphine by glia
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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.
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Within the compendium, fourteen studies had control groups that included six or more samples.
“Within our compendium, we identified a total of fourteen studies with control groups that included six or more samples5,6,15,49–59.”
From Confronting false discoveries in single-cell differential expression (2021) · cites this paper as [52]
The cited paper is one study, so it cannot establish the compendium-wide total of fourteen. For its own control group, STAR⋆METHODS reports four mock-treatment biological replicates in the single-cell analysis, not six or more samples; its bulk RNA-seq analysis reports three mock-treatment replicates. (LLM, conf=0.86)
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- Authors
- Avey, D., Sankararaman, S., Yim, A. K. Y., Barve, R., Milbrandt, J., & Mitra, R. D.
- Affiliations
- Washington University in St. Louis (US)
- Corresponding author
- Milbrandt, Jeffrey
- Mitra, Robi D.
- Venue
- Cell Reports
- Publisher
- Elsevier BV
- Published
- 2018-09
- Volume
- 24
- Issue
- 13
- Pages
- 3619-3629.e4
- ISSN
- 2211-1247 (ISSN-L)
- PMC
- PMC6357782
- OpenAlex
- W2893701755
- Cited by
- 143
- References
- 65
- Citations by year
- 2026: 10 · 2025: 9 · 2024: 17 · 2023: 32 · 2022: 20 · 2021: 13 · 2020: 27 · 2019: 14 · 2012: 1
- FWCI
- 5.15
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Cell Reports (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Digital Commons@Becker (Washington University School of Medicine) (submittedVersion, cc-by-nc-nd)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- NIH (CA009547-33, AGO13730, NS099314, 5U01MH109133, RF1MH117070, R01GM129126)
- Intellectual and Developmental Disabilities Research Center at Washington University (U54 HD087011)
- NCI (P30 CA091842)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Single-cell and spatial transcriptomics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Opioid Use Disorder Treatment
- Keywords
- morphine, opioid use disorder, glia, oligodendrocytes, astrocytes, nucleus accumbens, transcriptional response, p21, SGK1, oligodendrocyte maturation, myelination defects, unfolded protein response, cell type-specific gene expression
- MeSH terms
- Serum-Glucocorticoid Regulated Kinases, Analgesics, Opioid, Animals, Male, Mice, Inbred C57BL, Morphine, Neuroglia, Nucleus Accumbens, RNA, Messenger, Protein Serine-Threonine Kinases, Immediate-Early Proteins, Cyclin-Dependent Kinase Inhibitor p21, Mice, Single-Cell Analysis, Transcriptome
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