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

Area of Science:

• Neuroscience
• Stem Cell Biology
• Molecular Biology

Background:

• Cellular models are crucial for understanding neurodegenerative diseases like prion diseases.
• Investigating the molecular response of mesenchymal stem cells (MSCs) to prion exposure is vital for therapeutic development.

Purpose of the Study:

• To analyze gene expression changes in ovine bone marrow-derived MSCs (oBM-MSCs) exposed to scrapie brain homogenate.
• To identify genes and pathways involved in prion toxicity and MSCs' response to neuroinflammation.

Main Methods:

• RNA sequencing was performed on oBM-MSCs cultured under three conditions (scrapie homogenate, healthy homogenate, control) at 2 and 4 days post-inoculation.
• Differentially expressed genes (DEGs) were identified and enriched pathways were analyzed.
• RT-qPCR was used to validate the expression of selected DEGs.

Main Results:

• Significant differentially expressed genes (DEGs) were found in scrapie-treated oBM-MSCs, with more identified at 2 days post-inoculation.
• Enriched pathways were associated with prion toxicity and MSCs' response to the inflammatory environment.
• Seven out of eleven validated DEGs showed significant expression changes, confirming RNA-sequencing findings.

Conclusions:

• This study elucidates early molecular mechanisms of prion toxicity in MSCs.
• The findings contribute to understanding the response of MSCs to prion-induced neuroinflammation and may inform therapeutic strategies.