Modeling pain in vitro using nociceptor neurons reprogrammed from fibroblasts

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Modeling pain in vitro using nociceptor neurons reprogrammed from fibroblasts

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Title: Modeling pain in vitro using nociceptor neurons reprogrammed from fibroblasts
Author: Wainger, Brian J.; Buttermore, Elizabeth D.; Oliveira, Julia T.; Mellin, Cassidy; Lee, Seungkyu; Saber, Wardiya Afshar; Wang, Amy; Ichida, Justin K.; Chiu, Isaac M.; Barrett, Lee; Huebner, Eric A.; Bilgin, Canan; Tsujimoto, Naomi; Brenneis, Christian; Kapur, Kush; Rubin, Lee L.; Eggan, Kevin; Woolf, Clifford J.

Note: Order does not necessarily reflect citation order of authors.

Citation: Wainger, B. J., E. D. Buttermore, J. T. Oliveira, C. Mellin, S. Lee, W. A. Saber, A. Wang, et al. 2015. “Modeling pain in vitro using nociceptor neurons reprogrammed from fibroblasts.” Nature neuroscience 18 (1): 17-24. doi:10.1038/nn.3886. http://dx.doi.org/10.1038/nn.3886.
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Abstract: 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 cell classes but also the diversity of neuronal subtypes found in vivo and the pathophysiological changes that underlie specific clinical diseases. Here, we identify five transcription factors that reprogram mouse and human fibroblasts into noxious stimulus-detecting (nociceptor) neurons that recapitulate the expression of quintessential nociceptor-specific functional receptors and channels found in adult mouse nociceptor neurons as well as native subtype diversity. Moreover, the derived nociceptor neurons exhibit TrpV1 sensitization to the inflammatory mediator prostaglandin E2 and the chemotherapeutic drug oxaliplatin, modeling the inherent mechanisms underlying inflammatory pain hypersensitivity and painful chemotherapy-induced neuropathy. Using fibroblasts from patients with familial dysautonomia (hereditary sensory and autonomic neuropathy type III), we show that the technique can reveal novel aspects of human disease phenotypes in vitro.
Published Version: doi:10.1038/nn.3886
Other Sources: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4429606/pdf/
Terms of Use: This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAA
Citable link to this page: http://nrs.harvard.edu/urn-3:HUL.InstRepos:17820654
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