Selective conversion of fibroblasts into peripheral sensory neurons

Area of Science:

• Neuroscience
• Cell Biology
• Developmental Biology

Background:

• Peripheral sensory neurons are crucial for detecting stimuli like pain, itch, temperature, and proprioception.
• These neurons are functionally classified by their expression of TrkA, TrkB, or TrkC receptors.

Purpose of the Study:

• To develop a method for generating diverse human sensory neurons in vitro.
• To create a model system for studying sensory neuron function and for drug screening.

Main Methods:

• Transient co-expression of Brn3a with Ngn1 or Ngn2 in human and mouse fibroblasts.
• Characterization of induced sensory neurons (iSNs) for electrical activity, morphology, and gene expression.
• Calcium-imaging assays to assess functional responses to specific ligands.

Main Results:

• Fibroblasts were successfully reprogrammed into iSNs exhibiting properties of nociceptors, mechanoreceptors, and proprioceptors.
• iSNs displayed electrical excitability, characteristic neuronal morphology, and selective Trk receptor expression.
• Calcium imaging revealed functional responses in iSNs to ligands targeting pain- and itch-sensing pathways.

Conclusions:

• This reprogramming method provides a rapid and efficient way to generate genetically diverse human sensory neurons.
• The generated iSNs are suitable for drug screening and mechanistic studies of sensory neuron function.
• This approach advances the potential for in vitro modeling of sensory neuropathies and related conditions.