RT Journal Article
SR Electronic
T1 Single cell RNAseq uncovers a robust transcriptional response to morphine by oligodendrocytes
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 306944
DO 10.1101/306944
A1 Denis Avey
A1 Sumithra Sankararaman
A1 Aldrin K. Y. Yim
A1 Ruteja Barve
A1 Robi D. Mitra
A1 Jeffrey Milbrandt
YR 2018
UL http://biorxiv.org/content/early/2018/04/24/306944.abstract
AB 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 robust morphine-dependent changes in gene expression in 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 novel, morphine-dependent transcriptional response by oligodendrocytes that may contribute to the myelination defects observed in human opioid addicts.