title: Selective conversion of fibroblasts into peripheral sensory neurons.
abstract: Humans and mice detect pain, itch, temperature, pressure, stretch and limb position via signaling from peripheral sensory neurons. These neurons are divided into three functional classes (nociceptors/pruritoceptors, mechanoreceptors and proprioceptors) that are distinguished by their selective expression of TrkA, TrkB or TrkC receptors, respectively. We found that transiently coexpressing Brn3a with either Ngn1 or Ngn2 selectively reprogrammed human and mouse fibroblasts to acquire key properties of these three classes of sensory neurons. These induced sensory neurons (iSNs) were electrically active, exhibited distinct sensory neuron morphologies and matched the characteristic gene expression patterns of endogenous sensory neurons, including selective expression of Trk receptors. In addition, we found that calcium-imaging assays could identify subsets of iSNs that selectively responded to diverse ligands known to activate itch- and pain-sensing neurons. These results offer a simple and rapid means for producing genetically diverse human sensory neurons suitable for drug screening and mechanistic studies.
authors.affiliation: Department of Molecular and Cellular Neuroscience, Dorris Neuroscience Center, The Scripps Research Institute, La Jolla, California, USA.
authors.forename: Joel W
authors.initials: JW
authors.lastname: Blanchard
authors.affiliation: Department of Molecular and Cellular Neuroscience, Dorris Neuroscience Center, The Scripps Research Institute, La Jolla, California, USA.
authors.forename: Kevin T
authors.initials: KT
authors.lastname: Eade
authors.affiliation: 1] BioCircuits Institute, University of California San Diego, La Jolla, California, USA. [2] Balaton Limnological Institute of the Hungarian Academy of Sciences, Tihany, Hungary.
authors.forename: Attila
authors.initials: A
authors.lastname: Szűcs
authors.affiliation: Department of Molecular and Cellular Neuroscience, Dorris Neuroscience Center, The Scripps Research Institute, La Jolla, California, USA.
authors.forename: Valentina
authors.initials: V
authors.lastname: Lo Sardo
authors.affiliation: 1] Department of Molecular and Cellular Neuroscience, Dorris Neuroscience Center, The Scripps Research Institute, La Jolla, California, USA. [2] Neuroscience Graduate Program, University of California San Diego, La Jolla, California, USA.
authors.forename: Rachel K
authors.initials: RK
authors.lastname: Tsunemoto
authors.affiliation: Department of Molecular and Cellular Neuroscience, Dorris Neuroscience Center, The Scripps Research Institute, La Jolla, California, USA.
authors.forename: Daniel
authors.initials: D
authors.lastname: Williams
authors.affiliation: Molecular and Integrative Neurosciences Department, The Scripps Research Institute, La Jolla, California, USA.
authors.forename: Pietro Paolo
authors.initials: PP
authors.lastname: Sanna
authors.affiliation: 1] Department of Molecular and Cellular Neuroscience, Dorris Neuroscience Center, The Scripps Research Institute, La Jolla, California, USA. [2] Neuroscience Graduate Program, University of California San Diego, La Jolla, California, USA.
authors.forename: Kristin K
authors.initials: KK
authors.lastname: Baldwin
mesh_terms: D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000502:physiology; D005260:Female; D005347:Fibroblasts / Q000502:physiology* / Q000648:ultrastructure; D006801:Humans; D051379:Mice; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000502:physiology; D009619:Nociceptors / Q000648:ultrastructure; D018408:Patch-Clamp Techniques; D017933:Peripheral Nervous System / Q000166:cytology* / Q000648:ultrastructure; D011247:Pregnancy; D020812:Receptor, trkC / Q000235:genetics; D011984:Sensory Receptor Cells / Q000502:physiology* / Q000648:ultrastructure; D050819:Transcription Factor Brn-3A / Q000235:genetics / Q000502:physiology
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D009419:Nerve Tissue Proteins; D020812:Receptor, trkC; D050819:Transcription Factor Brn-3A; C105389:NEUROG1 protein, human; C491183:NEUROG2 protein, human; C102938:Neurog2 protein, mouse; C494188:POU4F1 protein, human; C494189:Pou4f1 protein, mouse; C486336:Neurog1 protein, mouse