Differential gene expression in human RAF1 S257L/+ and isogenic corrected iPSC-derived cardiomyocytes

Although several studies have uncovered abnormal signaling pathways in RASopathy disorders, little is known about the alterations of the cardiac transcriptome induced by Noonan syndrome (NS) mutations. Hence, to gain insights into the transcriptional alterations induced by the NS-associated RAF1S257L/+ mutation in human iPSC-derived cardiomyocytes, we performed quantitative transcriptome profiling by RNA-sequencing. Since we have found that inhibition of ERK5 and MEK1/2 pathways could normalized hypertrophy and myofibrillar disarray in mutant cardiomyocytes, we also aimed at identifying gene transcriptional profiles that were specifically affected by either MEK5-ERK5 or MEK1/2-ERK1/2 activation in RAF1S257L/+ iCMs. Overall design: mRNA profiles of human RAF1 S257L/+ and isogenic corrected iPSC-derived cardiomyocytes were generated by RNA-sequencing, in triplicate, using Ion S5.

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Jaffré F, Miller CL, Schänzer A, Evans T, Roberts AE, Hahn A, Kontaridis MI