Compositions and methods for making sensory neurons

Abstract

The three main peripheral sensory neuron (SN) subtypes, nociceptors, mechanoreceptors, and proprioceptors localize to dorsal root ganglia (DRG) and convey sensations such as pain, temperature, pressure and limb movement/position. Disclosed herein is a chemically defined differentiation protocol that generates all three SN subtypes from the same starting population, as well as methods to enrich for each individual subtypes. The protocol yields high efficiency and purity cultures that are electrically active and respond to specific stimuli. Their molecular character and maturity stage are described and evidence for their use as an axotomy model is exemplified. Cell populations and compositions formed from the resulting cells, as well as methods of their use for disease treatment, drug screening, and modeling of human disorders affecting SNs are also provided.