Modeling pain in vitro using nociceptor neurons reprogrammed from fibroblasts

摘要: Reprogramming somatic cells from one cell fate to another can generate specific neurons suitable for disease modeling. To maximize the utility of patient-derived neurons, they must model not only disease-relevant classes, but also diversity neuronal subtypes found in vivo and pathophysiological changes that underlie clinical diseases. We identified five transcription factors reprogram mouse human fibroblasts into noxious stimulus-detecting (nociceptor) neurons. These recapitulated expression quintessential nociceptor-specific functional receptors channels adult nociceptor as well native subtype diversity. Moreover, derived exhibited TrpV1 sensitization inflammatory mediator prostaglandin E2 chemotherapeutic drug oxaliplatin, modeling inherent mechanisms underlying pain hypersensitivity painful chemotherapy-induced neuropathy. Using patients with familial dysautonomia (hereditary sensory autonomic neuropathy type III), we technique was able reveal previously unknown aspects phenotypes vitro.