mRNA expression profiles of human iPSC-derived sensory neurons treated with paclitaxel, vincristine, bortezomib or cisplatin in the presence and absence of SP600125

For our investigation of the role of c-Jun in the underlying mechanisms of chemotherapy-induced peripheral neuropathy (CIPN), human iPSCs derived from patients were differentiated into sensory neurons and subsequently treated in vitro with four different chemotherapeutic drugs (paclitaxel, vincristine, bortezomib or cisplatin) in the presence and absence of small molecule inhibitor, SP600125. The transcriptomic analyses of such treated samples revealed upregulated transcription of c-Jun mRNA across the four drug types, which was reduced upon addition of SP600125. While this suggests the involvement of the JNK signalling pathway, detailed analyses of correlation coefficient revealed that a high correlation of c-Jun with neuronal injury, neuroinflammatory, metabolic and neuromodulation markers, thus identifying a central role of c-Jun in CIPN pathophysiology. Overall design: Human iPSC-derived sensory neurons (iPSC-DSN) were treated with 100nM of paclitaxel for 48h, or 50nM of vincristine for 16h, or 10nM of bortezomib for 16h, or 10µM of cisplatin for 16h, in combination with 10µM of SP600125, followed by RNA extraction.