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Selective conversion of fibroblasts into peripheral sensory neurons

Academic Article
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Overview

related to degree

  • Blanchard, Joel, Ph.D. in Biology, Scripps Research 2010 - 2016

authors

  • Blanchard, Joel
  • Eade, K. T.
  • Szucs, A.
  • Lo Sardo, V.
  • Tsunemoto, R. K.
  • Williams, D.
  • Sanna, Pietro
  • Baldwin, Kristin

publication date

  • 2015

journal

  • Nature Neuroscience  Journal

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.

subject areas

  • Animals
  • Basic Helix-Loop-Helix Transcription Factors
  • Female
  • Fibroblasts
  • Humans
  • Mice
  • Nerve Tissue Proteins
  • Nociceptors
  • Patch-Clamp Techniques
  • Peripheral Nervous System
  • Pregnancy
  • Receptor, trkC
  • Sensory Receptor Cells
  • Transcription Factor Brn-3A
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Identity

PubMed Central ID

  • PMC4466122

International Standard Serial Number (ISSN)

  • 1097-6256

Digital Object Identifier (DOI)

  • 10.1038/nn.3887

PubMed ID

  • 25420069
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Additional Document Info

start page

  • 25

end page

  • 35

volume

  • 18

issue

  • 1

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