RNA-sequencing transcriptomic analysis of scrapie-exposed ovine mesenchymal stem cells

This study explores the molecular mechanisms underlying prion toxicity and mesenchymal stem cell (MSC) responses using a cellular model of ovine bone marrow-derived MSCs (oBM-MSCs) exposed to scrapie brain homogenate. RNA-sequencing analysis was conducted on oBM-MSCs cultured under three conditions: exposed to scrapie-infected brain homogenate, healthy brain homogenate, and standard growth conditions, with samples collected at 2 and 4 days post-inoculation (dpi). Differentially expressed genes (DEGs) were identified, with the highest number observed at 2 dpi, coinciding with inoculum removal. Enriched pathways were associated with prion propagation, toxicity, and MSC responses to inflammatory environments. Validation by RT-qPCR of 11 selected DEGs confirmed significant expression changes in seven genes related to prion toxicity. These findings advance the understanding of the early molecular events in prion-induced toxicity and the inflammatory response of MSCs.