Differential Expression Analysis by RNA-Seq Reveals Perturbations in the Platelet mRNA Transcriptome Triggered by Pathogen Reduction Systems
2015 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 10, no 7, e0133070- p.Article in journal (Refereed) Published
Platelet concentrates (PCs) are prepared at blood banks for transfusion to patients in certain clinical conditions associated with a low platelet count. To prevent transfusion-transmitted infections via PCs, different pathogen reduction (PR) systems have been developed that inactivate the nucleic acids of contaminating pathogens by chemical cross-linking, a mechanism that may also affect platelets nucleic acids. We previously reported that treatment of stored platelets with the PR system Intercept significantly reduced the level of half of the microRNAs that were monitored, induced platelet activation and compromised the platelet response to physiological agonists. Using genome-wide differential expression (DE) RNA sequencing (RNA-Seq), we now report that Intercept markedly perturbs the mRNA transcriptome of human platelets and alters the expression level of greater than800 mRNAs (Pless than0.05) compared to other PR systems and control platelets. Of these, 400 genes were deregulated with DE corresponding to fold changes (FC) greater than= 2. At the p-value less than 0.001, as many as 147 genes were deregulated by greater than= 2-fold in Intercept-treated platelets, compared to none in the other groups. Finally, integrated analysis combining expression data for microRNA (miRNA) and mRNA, and involving prediction of miRNA-mRNA interactions, disclosed several positive and inverse correlations between miRNAs and mRNAs in stored platelets. In conclusion, this study demonstrates that Intercept markedly deregulates the platelet mRNA transcriptome, concomitant with reduced levels of mRNA-regulatory miRNAs. These findings should enlighten authorities worldwide when considering the implementation of PR systems, that target nucleic acids and are not specific to pathogens, for the management of blood products.
Place, publisher, year, edition, pages
Public Library of Science , 2015. Vol. 10, no 7, e0133070- p.
IdentifiersURN: urn:nbn:se:liu:diva-120648DOI: 10.1371/journal.pone.0133070ISI: 000358194900119PubMedID: 26172280OAI: oai:DiVA.org:liu-120648DiVA: diva2:847589
Funding Agencies|Regional Council of Ostergotland, Sweden [LIO-353011]; Canadian Blood Services/Canadian Institutes of Health Research (CIHR) Blood Utilization and Conservation Initiative via Health Canada 2015-08-202015-08-202016-02-22