Effect of in vitro dolutegravir exposure on transcriptome of oligodendrocyte precursor cells and oligodendrocytes

Bulk RNA sequencing revealed that dolutegravir exposure does not significantly alter the transcriptome of oligodendrocyte precursor cells compared to DMSO treatment. Conversely, we identified transcriptional changes after dolutegravir exposure in mature oligodendrocytes related to a variety of cellular mechanisms, including cellular responses to stress pathways, amino acid starvation, and mitochondrial dysfunction.

In particular, differential gene expression analyses revealed 127 significantly altered transcripts in dolutegravir treated oligodendrocytes, with 3 of these being Trib3, Atf4, and Cebpb, which have interconnected roles in regulating the integrated stress response.