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Single Cell RNAseq Uncovers a Robust Transcriptional Response to Morphine by Oligodendrocytes

35 Pages Posted: 8 Jun 2018 Publication Status: Published

See all articles by Denis Avey

Denis Avey

Washington University in St. Louis - Department of Genetics; Washington University in St. Louis - Center for Genome Sciences and Systems Biology

Sumithra Sankararaman

Washington University in St. Louis - Center for Genome Sciences and Systems Biology

Aldrin K. Y. Yim

Washington University in St. Louis - Department of Genetics

Ruteja Barve

Washington University in St. Louis - Genome Technology Access Center

Jeffrey Milbrandt

Washington University in St. Louis - Department of Genetics

Robi D. Mitra

Washington University in St. Louis - Department of Genetics; Washington University in St. Louis - Center for Genome Sciences and Systems Biology

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Abstract

Molecular and behavioral responses to opioids are thought to be primarily mediated by neurons, although there is accumulating evidence that other cell types also play a role in drug addiction. To investigate cell-type-specific opioid responses, we performed single-cell RNA sequencing of the nucleus accumbens of mice following acute morphine treatment. Differential expression analysis uncovered a surprisingly robust morphine-dependent transcriptional response by oligodendrocytes. We examined the expression of selected genes, including Cdkn1a and Sgk1, by FISH, confirming their induction by morphine in oligodendrocytes. Further analysis using RNAseq of FACS purified oligodendrocytes revealed a large cohort of morphine-regulated genes. Importantly, 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 shed light on a morphine-dependent transcriptional response by oligodendrocytes that may contribute to the myelination defects observed in human opioid addicts.

Suggested Citation

Avey, Denis and Sankararaman, Sumithra and Yim, Aldrin K. Y. and Barve, Ruteja and Milbrandt, Jeffrey and Mitra, Robi D., Single Cell RNAseq Uncovers a Robust Transcriptional Response to Morphine by Oligodendrocytes (2018). Available at SSRN: https://ssrn.com/abstract=3189384 or http://dx.doi.org/10.2139/ssrn.3189384
This version of the paper has not been formally peer reviewed.

Denis Avey

Washington University in St. Louis - Department of Genetics

4515 McKinley Ave
St. Louis, WA 63110
United States

Washington University in St. Louis - Center for Genome Sciences and Systems Biology

Saint Louis, MO
United States

Sumithra Sankararaman

Washington University in St. Louis - Center for Genome Sciences and Systems Biology

Saint Louis, MO
United States

Aldrin K. Y. Yim

Washington University in St. Louis - Department of Genetics

4515 McKinley Ave
St. Louis, WA 63110
United States

Ruteja Barve

Washington University in St. Louis - Genome Technology Access Center

Saint Louis, MO
United States

Jeffrey Milbrandt

Washington University in St. Louis - Department of Genetics ( email )

4515 McKinley Ave
St. Louis, WA 63110
United States

Robi D. Mitra (Contact Author)

Washington University in St. Louis - Department of Genetics ( email )

4515 McKinley Ave
St. Louis, WA 63110
United States

Washington University in St. Louis - Center for Genome Sciences and Systems Biology ( email )

Saint Louis, MO
United States

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